INTRODUCTION:Hydroxysafflor Yellow A (HSYA), known for its anti-inflammatory effects in cardiovascular diseases, has also been shown to reduce adiposity and improve metabolic disorders in diet-induced obese (DIO) mice. However, the molecular mechanisms underlying its anti-obesity effects, particularly whether they are mediated through immune-inflammatory pathways, remain unclear. This study aims to identify the key molecular mechanisms involved in HSYA's anti-obesity action. METHODS:Male C57BL/6J mice were divided into three groups: Standard Feed (SF), High-Fat Diet (HFD), and HFD with HSYA treatment (250 mg/kg/day for 9 weeks). Whole transcriptome sequencing of White Adipose Tissue (WAT) identified Differentially Expressed Genes (DEGs), which were integrated with network pharmacology predictions to identify key molecular targets of HSYA. RT-qPCR in WAT, 3T3-L1 adipocytes, and RAW264.7 macrophages validated the core genes, and molecular docking assessed HSYA's binding affinity with these targets. RESULTS:HSYA treatment significantly reduced body weight (35.27 ± 1.27g vs. 45.46 ± 1.68g, p < 0.05) and WAT mass (3.38±0.21g vs. 1.86±0.27g, p < 0.05) in DIO mice and ameliorated glucose and lipid metabolism abnormalities. Transcriptome analysis revealed 739 DEGs, with 21 overlapping genes identified between sequencing and network pharmacology analyses. Experimental validation highlighted Prkcd, Btk, and Vav1 as core genes within immune-inflammatory pathways, including chemokine and B cell receptor signaling, which are implicated in obesityrelated inflammation. RT-qPCR confirmed the downregulation of Prkcd, Btk, and Vav1 after HSYA treatment, consistent with transcriptomic findings. Molecular docking analysis demonstrated strong binding affinities between HSYA and VAV1 (-8.5 kcal/mol), BTK (-6.9 kcal/mol), and PRKCD (-6.6 kcal/mol). CONCLUSION:HSYA demonstrates the therapeutic potential for obesity by modulating immuneinflammatory pathways in WAT, specifically targeting Prkcd, Btk, and Vav1 in mice. Given its clinical use in cardiovascular disease, these findings suggest that HSYA may offer broader therapeutic benefits, including obesity management, though further studies are needed to clarify the mechanisms and assess its applicability to humans.

A four-year-old boy with X-linked hypohidrotic ectodermal dysplasia (XLHED) presented with complete anodontia, severe esthetic concerns, and functional limitations. The treatment plan aimed to provide both functional restoration and esthetic improvement, utilizing a fully digital workflow. After a comprehensive clinical and radiographic evaluation, digital cast scanning and 3D analysis were used to create a precise virtual plan for the fabrication of a customized complete denture. The initial dentures were followed by regular follow-up visits at 6-month intervals, with the patient returning for adjustments to accommodate his rapid growth. Over a five-year period of follow-up, the child received updated dentures as his facial and oral structures developed. This approach not only restored the boy's masticatory, speech, and esthetic functions but also allowed for continuous adaptation of the prostheses as the child grew. This report contributes to the existing literature by introducing a reproducible, quantitative workflow. Unlike purely descriptive digital denture reports, this protocol integrates a quantitative segmented morphometric analysis into a fully digital workflow to support objective, growth‑oriented clinical decision‑making, particularly in distinguishing between conservative relining and the need for complete prosthesis refabrication.

Discoidin domain receptors (DDRs) are nonintegrin collagen receptors which could be activated by various collagens. Overexpressed in numerous cancers, DDRs participate in tumorigenesis, tumor growth, dissemination, and metastasis. Immune checkpoint inhibitors (ICIs) have demonstrated low response rates in tumors such as head and neck cancer and pancreatic cancer, possibly due to the insufficient presence of effector T cells and the abundant collagen fibers in the tumor microenvironment. Recently, several studies indicate that DDRs account for ICIs resistance. For instance, DDR1 can prevent the anti-tumor immune responses via mediating the rearrangement of collagen fibers, increasing the secretion of interleukin-18 (IL-18) as well as facilitating the formation of neutrophil extracellular traps (NETs). DDR2 may participate in the establishment of immunosuppressive tumor microenvironment by recruiting myeloid-derived suppressor cells (MDSCs) and promoting the M2 polarization of macrophages. Notably, the interaction between collagens and immune cells also acts as a pivotal role in mediating tumor immune escape. Targeting DDRs and upstream regulators including collagen has been reported to significantly restore the antitumor immunity or inhibit tumor development, such as utilizing DDR1 inhibitors via AI screening from FDA-approved therapeutics or natural products, and strategies for collagen synthesis inhibition or collagen degradation. However, the above approaches are largely limited to preclinical studies and still warrant further validation in clinical trials. Based on the current evidences, DDRs serve as promising targets for improving the efficacy of ICIs against cancers; more studies are anticipated to reveal unclarified mechanisms of DDRs in regulating anti-tumor immunity.

Flowable composite resin and conventional composite resin are mainstream restorative materials for primary anterior strip crown restorations, yet dentists’ clinical utilization patterns, selection preferences, and underlying decision-making mechanisms remain underreported. This study aimed to investigate the types of resin materials selected by dentists engaged in pediatric dental practice, comprehensively analyze the underlying influencing reasons for material selection, including dentists’ cognition of material properties, operational difficulty, and clinical experience, to explore descriptive selection patterns and associated factors for clinical reference. From February to March 2025, a cross-sectional online questionnaire survey was conducted via WeChat professional networks. A total of 1260 dentists were invited, with 612 respondents and a response rate of 48.6

This study aimed to clarify the mechanobiological mechanisms of physiological root resorption in deciduous teeth, focusing specifically on how mechanical stress influences autophagy in periodontal ligament stem cells (PDLSCs) via the Piezo1 ion channel. We established a unilateral occlusal loading model in mice to simulate physiological mechanical stress, while in vitro studies utilized PDLSCs isolated from deciduous teeth at different resorption stages. Techniques included immunofluorescence staining for autophagy markers, Western blot analysis, Piezo1-specific pharmacological modulation, and transcriptome sequencing. Conditional Piezo1 knockout mice were generated to validate the mechanotransduction pathway. Our findings revealed distinct stage-dependent patterns in PDLSC behavior: early resorption stage (S-stage) cells maintained high autophagic activity with low IL-1β secretion, while mid-resorption stage (M-stage) cells showed Piezo1 upregulation and autophagy suppression. Mechanical stress was shown to inhibit autophagy through Piezo1-mediated activation of the PI3K/AKT pathway. Transgenic mouse models confirmed Piezo1’s essential role in mediating mechanical stress responses in periodontal tissue. The study establishes Piezo1 as a critical mechanotransducer that coordinates stage-specific autophagy regulation in PDLSCs through the PI3K/AKT signaling pathway. These findings suggest that controlled modulation of mechanical forces or Piezo1 activity could offer new therapeutic strategies for managing deciduous tooth exfoliation.

Osteoporosis (OP) is a growing global age-related metabolic bone disorder characterized by progressive bone loss, deteriorated trabecular microarchitecture, and elevated fragility fracture risk. Current first-line pharmacotherapies for OP are severely limited by long-term adverse events, narrow therapeutic windows, and failure to fully restore impaired bone homeostasis. Mesenchymal stem cell-derived small extracellular vesicles (sEVs) hold great promise for bone regenerative medicine, while their clinical translation for OP treatment is severely hampered by insufficient bone-targeting specificity and low in vivo bioavailability. Herein, we engineered a dual-functional cell-free nanoplatform based on sEVs derived from melatonin-preconditioned stem cells from human exfoliated deciduous teeth (SHED) with Angiopep-2 (Ang2pep) surface functionalization (M-Ang2pep-SHED-sEVs) for targeted OP therapy. Single-cell RNA sequencing (scRNA-seq) of clinical samples uncovered that impaired mitophagy and mitochondrial dysfunction are crucial hallmarks of osteoblasts in OP, and identified low-density lipoprotein receptor-related protein 1 (LRP1), the cognate receptor of Angiopep-2, as a membrane protein highly enriched in osteoblasts. Angiopep-2 surface modification conferred sEVs with enhanced osteoblast-targeting capacity, achieving an increase in bone tissue accumulation in vivo. Melatonin preconditioning optimized the protein cargo profile of sEVs, significantly enhancing their pro-osteogenic and mitophagy-regulating bioactivity without compromising targeting efficiency and biosafety. We further demonstrated that M-Ang2pep-SHED-sEVs effectively alleviated bone loss in ovariectomy-induced OP mouse models by increasing mitophagy to restore mitochondrial homeostasis and osteogenic function in impaired osteoblasts, which was validated by in vitro and in vivo loss-of-function assays. This work presents a promising, and targeted cell-free nanotherapeutic strategy for clinical OP management, and provides new insights into mitophagy-targeted therapy for metabolic bone diseases.

Turner teeth are developmental defects of permanent teeth commonly associated with disturbances affecting the corresponding primary predecessors, particularly infection or trauma. Although their clinical features have been described in previous reports, detailed histopathological characterization of severe Turner teeth, especially with respect to pulp tissue alterations, remains limited. This case-control study compared severe Turner teeth with normal teeth, focusing primarily on structural and molecular alterations in pulp tissue and descriptively on periodontal tissue morphology. Enamel structure and composition were not directly investigated. Ten extracted severe Turner teeth and ten extracted normal teeth from orthodontic patients were included. Hematoxylin and eosin staining and Masson trichrome staining were used to evaluate pulp, apical, and periodontal tissue morphology. Immunofluorescence staining was performed in pulp tissue sections to assess markers related to stemness (CD105), vascularization (CD31), innervation (βIII-tubulin), dentinogenesis (DSPP and RUNX2), extracellular matrix organization (Vimentin and FN1), inflammation (IL-1β and TNF-α), and Wnt/β-catenin signaling (β-catenin, AXIN1, and AXIN2). Compared with controls, severe Turner teeth showed a thinner odontoblast layer, a less continuous dentin-pulp interface, disorganized apical pulp fibers, reduced vascular distribution, irregular periodontal fiber arrangement, and a thinner cementum layer. In pulp tissue, CD105, CD31, βIII-tubulin, DSPP, RUNX2, Vimentin, FN1, and β-catenin expression levels were lower in Turner teeth, whereas IL-1β, TNF-α, AXIN1, and AXIN2 expression levels were higher (all P < 0.05). Severe Turner teeth were associated with coordinated histopathological alterations in pulp tissue architecture, marker expression, and periodontal morphology. These findings provide tissue-level evidence that severe Turner teeth are accompanied by an altered pulp microenvironment and provide a histopathological basis for future mechanistic and clinical studies.

The age-related decline in the pro-angiogenic capacity of mature dental pulp stem cells (DPSCs) severely limits pulp regeneration. We identify impaired glycolytic metabolism, driven by reduced glucose transporter type 1 (GLUT1) and hexokinase 2 (HK2) expression, as the key mechanism, as its inhibition diminished endothelial tube formation. To reverse this, we developed an aminolyzed highly branched poly(β-amino ester) (HBPA) as a vector for GLUT1/HK2 mRNA co-delivery, achieving >90% transfection efficiency with excellent biocompatibility. In vitro, conditioned medium from reprogrammed mature DPSCs resulted in a 2.0-fold increase in capillary length and a 2.3-fold increase in branch points, restoring angiogenic potential to levels equivalent to those of immature DPSCs. This efficacy translated robustly in vivo, where a tooth root slice model showed reprogrammed cells generated tissue with a vessel density of 10.2 vessels per mm2, 2.5-fold higher than that of untreated controls. Crucially, this level of vascularization was statistically indistinguishable from that achieved by the benchmark immature DPSCs. Our study demonstrates that HBPA-mediated metabolic reprogramming effectively rejuvenates mature DPSCs by restoring the “Metabolic-ECM-Angiogenesis Axis”, offering a translatable strategy for predictable, vascularized pulp regeneration.

Protein kinases play crucial roles in tumor progression and modulation of the immunosuppressive tumor microenvironment. However, the specific function of MASTL (microtubule-associated serine/threonine kinase-like) in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we integrated multi-omics bioinformatic analyses with experimental validation to delineate the clinical significance and biological role of MASTL in LUAD. We found that MASTL is markedly overexpressed in LUAD tissues and exhibits substantial diagnostic value. Elevated MASTL expression served as an independent prognostic indicator of poor overall survival, particularly in early-stage patients. Comprehensive immune profiling revealed a strong association between high MASTL expression and an immunosuppressive tumor microenvironment, characterized by impaired dendritic cell function and altered Th1/Th2 balance. Notably, patients with low MASTL expression showed enhanced sensitivity to immune checkpoint blockade therapy. Phosphoproteomic analysis identified serine 370 (S370) as a novel functional phosphorylation site on MASTL, whose activation correlated with higher tumor grade and dysregulation of key oncogenic pathways, including p53, MYC, mTOR, WNT, and HIPPO signaling. Functionally, pharmacological inhibition of MASTL using MKI-1 suppressed LUAD cell proliferation, induced apoptosis and cell cycle arrest, and reduced cancer stem cell-like properties such as self-renewal and metastatic potential. Importantly, MKI-1 administration significantly inhibited tumor growth in a LUAD xenograft model with good tolerability. Collectively, our findings identify MASTL as a pivotal regulator of tumor progression and immune evasion in LUAD and underscore its potential as both a prognostic biomarker and a promising therapeutic target.

INTRODUCTION:Nuciferine, the key aporphine alkaloid compound extracted from lotus leaf, has demonstrated remarkable effects in the prevention of obesity. Our current study sought to elucidate the exact mechanisms of the protective roles of nuciferine on obesity and associated metabolic abnormalities. METHODS:Male C57BL/6J mice were given a high-fat diet (HFD) containing 0.10% nuciferine for 12 weeks. Body weight and epididymal white adipose tissue (eWAT) mass were collected. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were conducted. A multidisciplinary approach, including transcriptomic analysis and network pharmacology, was employed to identify novel targets and signaling pathways of nuciferine in obesity prevention, which were further confirmed using real-time quantitative polymerase chain reaction (RT-qPCR), molecular docking, and in vitro cell experiments performed in RAW 264.7 macrophages. RESULTS:Nuciferine dramatically reduced the weight gain and eWAT mass and ameliorated glucose tolerance, insulin sensitivity, and inflammation in adipose tissue of HFD-fed mice. In fully differentiated 3T3-L1 adipocytes, nuciferine prevented palmitic acid (PA)-induced intracellular lipid accumulation, as evidenced by Oil Red O staining and triglyceride (TG) determination. Integration of transcriptomic sequencing in eWAT and network pharmacology identified 15 target genes, including LGALS3, CTSB, and RBP4, and 5 signaling pathways, including cAMP and Rap1 signaling pathways, which were primarily associated with inflammation. Further studies confirmed that nuciferine decreased LGALS3, CTSB, and RBP4 mRNA expression in eWAT of HFD-fed mice. Additionally, nuciferine inhibited mRNA expression of pro-inflammatory cytokines IL-6, along with LGALS3, CTSB, and RBP4 in lipopolysaccharide-treated RAW 264.7 macrophages. Molecular docking showed that nuciferine had strong binding ability to LGALS3, CTSB, and RBP4. CONCLUSION:These findings suggest that nuciferine may reduce adipose tissue inflammation by inhibiting mRNA levels of macrophage inflammation-associated genes LGALS3, CTSB, and RBP4, thereby protecting against obesity and associated metabolic inflammation.

BackgroundHead and neck squamous cell carcinoma (HNSCC) faces challenges with limited immune checkpoint inhibitors (ICIs) efficacy. This study identifies NLRX1, highly expressed in HNSCC tumor cells, as a key driver of immune evasion and ICIs’ resistance.MethodsThis study investigated the role of NLRX1 in HNSCC immune evasion and ICIs resistance. We performed retrospective analyses on patient cohorts to correlate NLRX1 expression with clinical outcomes. Bioinformatic analyses and immunofluorescence staining of human HNSCC tissues were employed to assess associations between immune cell infiltration, gene expression correlations and PD-L1 levels on antigen-presenting cells (APCs). In vitro experiments were conducted to investigate the regulatory role of NLRX1 on cell proliferation and gene expression profiling by overexpressing or knocking down NLRX1. In vivo studies of subcutaneous tumor models in both immunodeficient and immunocompetent mice were utilized to assess the function of NLRX1 on tumor progression.ResultsThe expression NLRX1 is correlated with unfavorable patient outcomes. NLRX1 promotes tumor progression by modulating the immune microenvironment, not directly affecting tumor cell proliferation. Mechanistically, NLRX1 suppresses the type I interferon (IFN-I) pathway by inhibiting STING expression in HNSCC. Notably, tumor cell-intrinsic NLRX1 negatively correlates with PD-L1 expression on APCs in HNSCC. In vivo, NLRX1 knockdown activated STING-IFN-I signaling, upregulated APC PD-L1, suppressed tumor growth, and significantly boosted anti-PD-L1 therapy in murine tumor models.ConclusionsNLRX1 mediates immune evasion in HNSCC by downregulating STING protein abundance, suppressing the IFN-I pathway, and decreasing PD-L1 expression of APCs. Targeting NLRX1 offers a promising strategy to overcome ICI resistance and improve immunotherapeutic efficacy in HNSCC.

Objective: Multiple programmed cell death (PCD) pathways have been individually reported to be triggered by cisplatin, but whether and how they are co-regulated remains unclear. In this study, we comprehensively investigate the spectrum of cisplatin-induced PCD. Methods: We employed integrated in vitro and in vivo models, including human cancer cell lines, a Cal27 xenograft mouse model, and paired clinical specimens from an oral squamous cell carcinoma patient receiving neoadjuvant cisplatin-based chemotherapy. A comprehensive methodological suite-encompassing cell death assays, Western blotting, Hematoxylin and eosin staining, immunofluorescence, Cyclic multiplexed tissue staining, and pathway-specific pharmacological inhibitors was utilized to dissect the activation of apoptosis, necroptosis, pyroptosis, and ferroptosis. Results: Cisplatin simultaneously upregulates markers of PCD pathways (including apoptosis, necroptosis, pyroptosis, and ferroptosis) in a dose- or time-dependent manner. Pharmacological inhibition or genetic knockdown of key genes in each pathway significantly reduced cytotoxicity, confirming their functional roles. Notably, indicators of key pro-inflammatory death modalities, pyroptosis and ferroptosis, were prominently co-upregulated in both xenograft tumors and clinical patient samples, suggesting that these two forms of PCD may represent the predominant death forms in cisplatin-induced tumor cell death. Conclusion: Cisplatin induces the coordinated activation of multiple cell death programs within a unified framework. Prominent engagement of immunogenic cell death pathways, particularly pyroptosis and ferroptosis, provides a mechanistic basis for the clinically observed synergy between cisplatin and immune checkpoint blockade therapy.

Abstract X-linked hypophosphatemia (XLH) is a hereditary disorder caused by dysregulation of the FGF23-kidney-bone/teeth axis, leading to chronic hypophosphatemia and impaired mineralization. As target organs highly sensitive to phosphate homeostasis, the teeth and jaw often exhibit pathological changes that precede skeletal deformities, offering early diagnostic value. This article elucidates the damaging effects of hypophosphatemia on dental hard tissues and craniofacial development. Hypophosphatemia-induced impaired dentin mineralization results in interglobular dentin retention and abnormal pulp morphology, which, together with enamel microcracks, constitute the pathological basis for spontaneous pulp infections and periapical lesions. Craniofacial manifestations also include jaw abnormalities, periodontal bone loss, and craniosynostosis. A diagnostic framework for XLH-related oral manifestations integrating imaging, biochemical markers, and genetic testing is proposed, with key differential diagnoses clarified. The article emphasizes the paradigm shift in managing XLH-associated oral complications from conventional phosphate/vitamin D supplementation to anti-FGF23 targeted therapy. It advocates for life-cycle oral management coordinated with systemic homeostatic reconstruction for XLH encompassing prevention, infection control, and multidisciplinary care. By integrating systemic etiological intervention with local precision therapy, this review aims to provide a basis for early identification and standardized management of XLH.

Proteasome activator 28 subunit gamma (PA28γ) attracts considerable attention for its ability to regulate multiple molecules involved in tumor progression. However, its intrinsic activation and functional regulatory mechanisms in the regulation of tumor growth remain incompletely understood. Here, using head and neck squamous cell carcinoma (HNSCC) as a model, we identify phosphorylation at the T23 site of PA28γ, a modification that is highly expressed across pan-cancer types and associated with poor prognosis. Notably, phosphorylation-deficient PA28γ-T23 mutant mice exhibit resistance to carcinogen-induced HNSCC tumors, whereas the phosphomimetic PA28γ-T23 mutant promotes tumor formation and progression. We subsequently explore the underlying mechanism and find that casein kinase 2 (CK2) mediates PA28γ-T23 phosphorylation, which regulates the abundance of growth-related E4F transcription factor 1 (E4F1) through the PA28γ-proteasome pathway. These findings highlight PA28γ-T23 phosphorylation as a crucial pro-oncogenic signal and an unfavorable prognostic indicator across various cancers and underscore its potential as a target for early cancer intervention and treatment. Dysregulation in the proteasome pathway contributes to the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Here the authors identify that Casein kinase 2 (CK2) mediates phosphorylation of Proteasome activator 28 subunit gamma (PA28γ), which promotes tumor formation and progression in HNSCC mouse models.

To evaluate the clinical efficacy of an autonomous robotic system in reducing bone resection volume and operative time for impacted teeth extraction in children, compared to conventional surgical techniques. A single-blinded randomized controlled trial enrolled 10 pediatric patients impacted teeth. Each participant received robotic surgery (test group) and conventional surgery (control group) on contralateral quadrants. Primary outcomes were bone resection volume ratio (measured via pre-/post-op CBCT segmentation) and operative time. Secondary outcomes included nerve injury incidence and healing outcomes. Differences were analyzed via paired t-tests and generalized estimating equations. In this RCT of 10 children with impacted teeth, robotic surgery reduced total operative time by 35

BackgroundManagement of compound odontomas in the pediatric anterior mandible poses significant surgical challenges due to proximity to developing tooth follicles and neurovascular structures. Conventional enucleation risks iatrogenic injury to adjacent dentoalveolar anatomy, while suboptimal bone preservation may impede permanent tooth eruption.Case descriptionAn 8-year-old patient presented with a compound odontoma adjacent to the unerupted permanent mandibular incisor. Utilizing an autonomous robotic guidance system independently developed by our research group, we performed minimally invasive enucleation featuring: (1) virtual osteotomy pathway planning, (2) sub-millimeter precision bone removal preserving the follicular space of tooth 31, and (3) capsule dissection under optical navigation. At the 2-week follow-up, the surgical site demonstrated complete mucosal healing without neurosensory complications, and CBCT confirmed absence of residual pathology.ConclusionRobotic-assisted enucleation enabled tissue-preserving removal of a high-risk odontoma while maintaining eruption potential. This approach represents a paradigm shift toward precision-targeted dentoalveoral surgery, particularly valuable for anatomically complex pediatric cases.Clinical Trial Registrationidentifier [ChiCTR2400092822].

OBJECTIVES:This study aimed to explore the clinical efficacy of severe early childhood caries (SECC) treatment combined with local anesthesia under general anesthesia. METHODS:A total of 108 children under 6 years old who underwent SECC dental treatment under general anesthesia at the Department of Pediatric Dentistry, Third Affiliated Hospital of Air Force Medical University from March to December 2023 were selected as the study subjects, with American Society of Anesthesiologists (ASA) classification of classⅠor Ⅱ. The study subjects were divided into a control group (n=54) and an experimental group (n=54) by retrieving intraoperative cases and postoperative follow-up records. The control group was given general anesthesia through inhalation combined with nasotracheal intubation, whereas the experimental group was given local anesthesia with 2% lidocaine on each treated tooth on the basis of general anesthesia. The basic information, preoperative anesthesia depth, hemodynamic changes during different surgical procedures, postoperative pain, and adverse reactions in the two groups were recorded and analyzed. RESULTS:No statistically significant difference was found in the basic information and preoperative anesthesia depth between the two groups (P>0.05). Among the three procedures (pulpotomy, root canal treatment, and tooth extraction), the three observed indicators in the experimental group were significantly lower than those in the control group (P<0.05). The proportion of patients in the experimental group who needed to take analgesic measures in accordance with the modified facial pain scale (FPS-R) score was significantly lower than that in the control group at postoperative wakefulness and 2 h after surgery (P<0.05). Meanwhile, no statistically significant difference was observed between the groups at 24 h after surgery (P>0.05). The proportion of patients in the experimental group who needed to take analgesic measures on the basis of the parent posto-perative pain measurement (PPPM) score was significantly lower than that in the control group when they were awake after surgery (P<0.05). No statistically significant difference was found between the groups at 2 and 24 h after surgery (P>0.05). Moreover, no statistically significant difference was observed in the incidence of adverse reactions between the two groups at 24 h after surgery (P>0.05). CONCLUSIONS:The combination of local anesthesia during SECC dental treatment under general anesthesia results in minimal changes in intraoperative hemodynamics and mild postoperative pain response, hence worthy of clinical promotion.

Epithelial homeostasis ensures that the epithelium can perform its normal physiological functions. Mechanical signaling response through integrin-mediated adhesions of the basement membrane (BM) is crucial for maintaining epithelial homeostasis. The essential mechanosensors YAP and the paralog TAZ (YAP/TAZ) have been shown to play a critical role in epithelial homeostasis, but the key regulator that mediates mechanical signaling to YAP/TAZ in maintaining epithelial homeostasis has not been fully understood. In this study, we noticed that mechanical signals correlated with YAP/TAZ activation and basal state maintenance in epithelial stem/progenitor cells through immunohistochemistry. Subsequently, we found that inhibition of focal adhesion kinase (FAK) suppressed YAP/TAZ activation in the human keratinocyte line HaCaT cells. Furthermore, inhibition of the interaction between YAP/TAZ and the transcriptional enhanced associate domains (TEADs) resulted in the differentiation of HaCaT cells. Finally, we used primary mouse epithelial cells to reconstruct the epithelium in vitro and found that FAK inhibition led to both a reduction in YAP/TAZ activity and an increase of differentiation in the basal layer cells. In conclusion, our findings reveal that FAK mediates mechanical signaling to maintain epithelial homeostasis via YAP/TAZ-TEADs.

Objectives This study evaluates Fasudil, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, for its potential to inhibit oral squamous cell carcinoma (OSCC) growth and explores phospho-cofilin as a potential biomarker for prediction treatment efficiency of Fasudil in OSCC. Design A cohort of 109 OSCC patients provided tissue samples for phospho-cofilin expression analysis and survival analysis. The study examined the effect of Fasudil on OSCC cell lines HSC-3, UM1, and CAL33, assessing tumor growth inhibition through various in vitro and in vivo experiments. ROCK inhibition response and downstream mechanisms were explored by RNA sequencing, q-PCR, and immunofluorescence. Results High phospho-cofilin expression in OSCC tissues correlated with poor patient outcomes and was a reliable biomarker for ROCK activity. Fasudil inhibited growth in OSCC cell lines, particularly those with high phospho-cofilin expression. ROCK inhibition led to downregulation of Yes-associated protein (YAP) activity, resulting in suppressed tumor proliferation and increased apoptosis both in vitro and in vivo. Conclusions Inhibition of ROCK/phospho-cofilin/YAP by Fasudil could suppress OSCC proliferation, while phospho-cofilin served as a potential biomarker of OSCC.

Despite significant progress in characterizing the omics landscape of head and neck squamous cell carcinoma (HNSCC), the development of precision therapies remains limited. One key factor contributing to this challenge is the marked molecular heterogeneity of HNSCC. Further investigation of molecular profiles within HNSCC may facilitate the improvement in more effective precision treatments. Here, we focus on the dysregulation of PDZ and LIM domain protein 3 (PDLIM3) in HNSCC. The expression levels of PDLIM3 were analyzed using public datasets to assess its potential role in tumor progression. We found that PDLIM3 was downregulated in pan-cancer and HNSCC. The prognostic significance of PDLIM3 was evaluated through tissue microarray, and the downregulation of PDLIM3 was correlated with poor HNSCC prognosis. Investigating the implications of PDLIM3 for tumor metastatic ability in vitro, we found that PDLIM3 suppressed the migration and invasion of HNSCC, accompanied by partially impeding the process of epithelial-mesenchymal transition (EMT). Furthermore, PDLIM3 inhibited the transcriptional activity of Yes-associated protein (YAP), suggesting that YAP may be involved in the PDLIM3-mediated suppression of HNSCC metastatic ability. Our findings identify a potential signaling axis wherein PDLIM3 regulates YAP-EMT, thereby influencing tumor metastatic ability, and suggest the potential role of PDLIM3 as a tumor suppressor and prognostic biomarker for HNSCC.