Turning foes to friends: Advanced "in situ nanovaccine" with dual immunoregulation for enhanced immunotherapy of metastatic triple-negative breast cancer.

As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

Advancing dentin remineralization: Exploring amorphous calcium phosphate and its stabilizers in biomimetic approaches.

OBJECTIVE: This review elucidates the mechanisms underpinning intrafibrillar mineralization, examines various amorphous calcium phosphate (ACP) stabilizers employed in dentin's intrafibrillar mineralization, and addresses the challenges encountered in clinical applications of ACP-based bioactive materials. METHODS: The literature search for this review was conducted using three electronic databases: PubMed, Web of Science, and Google Scholar, with specific keywords. Articles were selected based on inclusion and exclusion criteria, allowing for a detailed examination and summary of current research on dentin remineralization facilitated by ACP under the influence of various types of stabilizers. RESULTS: This review underscores the latest advancements in the role of ACP in promoting dentin remineralization, particularly intrafibrillar mineralization, under the regulation of various stabilizers. These stabilizers predominantly comprise non-collagenous proteins, their analogs, and polymers. Despite the diversity of stabilizers, the mechanisms they employ to enhance intrafibrillar remineralization are found to be interrelated, indicating multiple driving forces behind this process. However, challenges remain in effectively designing clinically viable products using stabilized ACP and maximizing intrafibrillar mineralization with limited materials in practical applications. SIGNIFICANCE: The role of ACP in remineralization has gained significant attention in dental research, with substantial progress made in the study of dentin biomimetic mineralization. Given ACP's instability without additives, the presence of ACP stabilizers is crucial for achieving in vitro intrafibrillar mineralization. However, there is a lack of comprehensive and exhaustive reviews on ACP bioactive materials under the regulation of stabilizers. A detailed summary of these stabilizers is also instrumental in better understanding the complex process of intrafibrillar mineralization. Compared to traditional remineralization methods, bioactive materials capable of regulating ACP stability and controlling release demonstrate immense potential in enhancing clinical treatment standards.

Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice.

BACKGROUND: Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. MATERIALS AND METHODS: To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. RESULTS: Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. CONCLUSIONS: Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

Adhesive hydrogel releases protocatechualdehyde-Fe3+ complex to promote three healing stages for accelerated therapy of oral ulcers.

Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.

Revisited and innovative perspectives of oral ulcer: from biological specificity to local treatment.

Mouth ulcers, a highly prevalent ailment affecting the oral mucosa, leading to pain and discomfort, significantly impacting the patient's daily life. The development of innovative approaches for oral ulcer treatment is of great importance. Moreover, a deeper and more comprehensive understanding of mouth ulcers will facilitate the development of innovative therapeutic strategies. The oral environment possesses distinct traits as it serves as the gateway to the digestive and respiratory systems. The permeability of various epithelial layers can influence drug absorption. Moreover, oral mucosal injuries exhibit distinct healing patterns compared to cutaneous lesions, influenced by various inherent and extrinsic factors. Furthermore, the moist and dynamic oral environment, influenced by saliva and daily physiological functions like chewing and speaking, presents additional challenges in local therapy. Also, suitable mucosal adhesion materials are crucial to alleviate pain and promote healing process. To this end, the review comprehensively examines the anatomical and structural aspects of the oral cavity, elucidates the healing mechanisms of oral ulcers, explores the factors contributing to scar-free healing in the oral mucosa, and investigates the application of mucosal adhesive materials as drug delivery systems. This endeavor seeks to offer novel insights and perspectives for the treatment of oral ulcers.

Ultrahigh Energy Storage Density and Efficiency in Orthorhombic PLZST Antiferroelectric Ceramics via Composition Regulation.

PbZrO3-based antiferroelectric (AFE) ceramic materials have emerged as potential candidates for the next generation of high-energy multilayer ceramic capacitors (MLCCs) because of their distinctive characteristics of double hysteresis loops. The energy storage efficiency of orthorhombic AFE ceramics with ultrahigh storage density is relatively low, which hinders their practical application. In this study, the low efficiency limit of PLZST-based orthorhombic ceramics was overcome by precisely adjusting the Sn4+ content in the (Pb0.95Ca0.02La0.02)(Zr0.99-xSnxTi0.01)O3 AFE ceramics. On one hand, the addition of Sn4+ disrupts the original long-range dipole and improves the rapid response of polarization reversal under the applied voltage. As a result, the difference in electric hysteresis under an electric field is reduced, leading to a significant improvement in energy storage efficiency. On the other hand, increasing the Sn4+ content suppresses the formation of oxygen vacancies, inhibiting grain growth and strengthening grain bonding. This results in ceramics with a high breakdown field strength. Ultimately, the resulting PLCZST ceramics reveal an expressively improved recoverable energy density of 10.2 J cm-3 together with a high energy efficiency of 91.4% under a high applied electric field of 560 kV cm-1. The present study demonstrates the tunability of performance in orthorhombic PLZST AFE ceramics, thereby introducing a ceramic material with exceptional energy storage capabilities for MLCC applications.

Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment.

ABSTARCT: Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.

Research progress on the mechanical compatibility of restorative materials with dental tissue / 口腔疾病防治

@#As the main means of mastication, teeth can withstand countless functional contacts. The mechanical properties of teeth are closely related to their tissue structure. Enamel and dentin have a high hardness and modulus of elasticity, and their graded structure allows them to withstand bite forces without being susceptible to fracture. When tooth tissue is defective, full crown restoration is often needed to restore the normal shape and function of the tooth. Metal materials, ceramic materials, and polyetheretherketone (PEEK) materials are commonly used for crown restoration. Metal materials have certain disadvantages in terms of aesthetics and are relatively rarely used in clinical practice. Ceramic materials with different compositions exhibit differences in performance and aesthetics, but their elastic modulus and hardness are much higher than those of dental tissue, resulting in mismatching mechanical properties. In contrast, the elastic modulus of PEEK is lower than that of tooth tissue and similar to that of bone tissue, but its properties can be improved by fiber reinforcement. Notably, when the mechanical properties of a restoration material and tooth tissue are not fully matched, the interface between them often forms a potential weak link, which ultimately affects the stability and long-term effect of the restoration. This article introduces the mechanical properties and corresponding structural characteristics of enamel and dentin. On this basis, the advantages and limitations of existing restoration materials are analyzed, and the possibility of biomimetic design of full crowns is further explored.

Mannose-doped metal-organic frameworks induce tumor cell pyroptosis via the PERK pathway.

BACKGROUND: The implementation of pyroptosis exhibits significant potential as a tactic to enhance tumor immune microenvironments. Previous applications of pyroptosis inducers have encountered various limitations, such as the development of drug resistance, manifestation of toxic side effects, and a deficiency in targeting capabilities. As a result, there is a growing demand for tumor therapeutic molecules that can overcome these obstacles. Therefore, the objective of this study is to develop a multifunctional nanospheres that addresses these challenges by enabling high-precision targeting of tumor cells and inducing effective pyroptosis. RESULTS: We prepared a mannose-modified MOF called mannose-doped Fe3O4@NH2-MIL-100 (M-FNM). M-FNM could enter CAL27 cells through MR-mediated endocytosis, which caused in a significant increase in the level of intracellular ROS. This increase subsequently triggered ER stress and activated the PERK-eIF2α-ATF4-CHOP signaling pathway. CHOP then mediated the downstream cascade of Caspase-1, inducing pyroptosis. In in vivo experiments, M-FNM demonstrated excellent targeting ability and exhibited anti-tumor effects. Additionally, M-FNM reshaped the immune microenvironment by promoting the infiltration of anti-tumor immune cells, primarily T lymphocytes. CONCLUSIONS: M-FNM significantly decreased tumor growth. This novel approach to induce pyroptosis in tumor cells using M-FNM may offer new avenues for the development of effective immunotherapies against cancer.

Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

BMP signaling in the development and regeneration of tooth roots: from mechanisms to applications.

Short root anomaly (SRA), along with caries, periodontitis, and trauma, can cause tooth loss, affecting the physical and mental health of patients. Dental implants have become widely utilized for tooth restoration; however, they exhibit certain limitations compared to natural tooth roots. Tissue engineering-mediated root regeneration offers a strategy to sustain a tooth with a physiologically more natural function by regenerating the bioengineered tooth root (bio-root) based on the bionic principle. While the process of tooth root development has been reported in previous studies, the specific molecular mechanisms remain unclear. The Bone Morphogenetic Proteins (BMPs) family is an essential factor regulating cellular activities and is involved in almost all tissue development. Recent studies have focused on exploring the mechanism of BMP signaling in tooth root development by using transgenic animal models and developing better tissue engineering strategies for bio-root regeneration. This article reviews the unique roles of BMP signaling in tooth root development and regeneration.

Applicative Assessment of a Selective Laser Melting 3D-Printed Ti-6Al-4 V Plate with a Honeycomb Structure in the Reconstruction of a Mandibular Defect of a Beagle Dog.

The most challenging problem in oral and maxillofacial surgery is the reconstruction of defects for the oral and maxillofacial complex. Transfer of different autografts is known as the "gold standard" for the reconstruction of bone defects in the oral and maxillofacial region. Graft harvesting, however, can lead to many complications, such as donor-site morbidity, surgical time-consuming, etc. Three-dimensional (3D) printing technology is an innovative technique that allows the fabrication of personalized plates and scaffolds to fit the precise anatomy of an individual's defect. In this study, a selective laser melting 3D-printed Ti-6Al-4 V plate with a honeycomb was designed, and its physical and biological features were characterized. The personalized 3D-printed scaffold and commercialized titanium reconstruction plate were applied to reconstruct a 4 cm mandibular defect in a beagle dog. Effects of the treatment were analyzed radiologically and histologically. Our results showed that the application of a 3D-printed plate with a honeycomb achieved good biocompatibility and osseointegration and has potential clinical application.

Carbon Dots as Potential Therapeutic Agents for Treating Non-Alcoholic Fatty Liver Disease and Associated Inflammatory Bone Loss.

Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most significant metabolic diseases worldwide and is associated with heightened systemic inflammation, which has been shown to foster the development of extrahepatic complications. So far, there is no definitive, effective, and safe treatment for NAFLD. Although antidiabetic agents show potential for treating NAFLD, their efficacy is significantly limited by inadequate liver accumulation at safe doses and unwanted side effects. Herein, we demonstrate that pharmacologically active carbon dots (MCDs) derived from metformin can selectively accumulate in the liver and ameliorate NAFLD by activating hepatic PPARα expression while maintaining an excellent biosafety. Interestingly, MCDs can also improve the function of extrahepatic organs and tissues, such as alleviating alveolar inflammatory bone loss, in the process of treating NAFLD. This study proposes a feasible and safe strategy for designing pharmacologically active MCDs to target the liver, which regulates lipid metabolism and systemic inflammation, thereby treating NAFLD and its related extrahepatic complications.

[Oral Squamous Cell Carcinoma-Derived Cell-Free DNA Modulates Stemness and Migration of Oral Squamous Cell Carcinoma Cell Line by Inducing M2 Macrophage Polarization].

Objective: To investigate the effect of oral squamous cell carcinoma (OSCC)-derived cell-free DNA (cfDNA) on the polarization of macrophages and the regulatory effect of polarized macrophages on the stemness and migration of OSCC cells. Methods: A total of 30 OSCC tissue samples, 10 dysplastic oral tissue samples, and 10 normal oral tissue samples were collected. The status of all tissue samples was confirmed by pathology analysis. Immunohistochemical (IHC) staining and immunofluorescence (IF) staining were performed to examine the cell count and location of M2 macrophages in different types of oral tissue samples. The conditioned medium (CM) of OSCC cell line CAL-27 from the human tongue was collected and the cfDNA was concentrated and isolated for identification. The macrophages were treated by cfDNA and their morphological characteristics were observed under microscope. The expression levels of polarization-related indicators were determined by RT-qPCR. CAL-27 cell line was treated with macrophage CM induced by cfDNA and the expression levels of stemness-related genes were determined by RT-qPCR. Scratch-wound assay was conducted to verify that the migration ability of CAL-27 was modulated by macrophages induced by cfDNA. Results: There were more M2 macrophages in the deep connective tissue of dysplastic oral epithelium and the stroma of OSCC compared with those in the normal oral tissues ( P<0.05). OSCC cell line CAL-27 could secret cfDNA of 10000-15000 bp in length. cfDNA secreted by CAL-27 could induced in macrophages significantly higher expression of M2-macrophage-related genes ( P<0.05). cfDNA-treated macrophages induced significantly increased expression of stemness-related genes in CAL-27 cell line ( P<0.05) and promoted the migration ability of CAL-27 cell line ( P<0.05). Conclusion: OSCC-derived cfDNA promotes stemness and migration of OSCC cell line by inducing M2 macrophage polarization.

Piezo1 mediates the degradation of cartilage extracellular matrix in malocclusion-induced TMJOA.

OBJECTIVES: To evaluate the role of Piezo1 in the malocclusion-induced osteoarthritic cartilage of the temporomandibular joint. METHODS: A temporomandibular joint osteoarthritis model was established using a unilateral anterior crossbite in vivo, and cartilage degeneration and Piezo1 expression were observed by histological and immunohistochemical staining. ATDC5 cells were loaded with 24 dyn/cm2 fluid flow shear stress using the Flexcell device in vitro and expression and function of Piezo1 were evaluated. After identifying the function of Piezo1 in YAP translocation under FFSS conditions, the influence of Piezo1 and YAP on metabolism-related enzymes under FFSS was detected through a real-time polymerase chain reaction analysis and western blotting. A UAC-TMJ injection model was established to observe the therapeutic effect of intra-articular injection of a Piezo1 inhibitor on osteoarthritic cartilage matrix loss. RESULTS: Piezo1 was overexpressed in the osteoarthritic cartilage and cultured chondrocytes under shear stress. Piezo1 Silencing inhibited the nuclear translocation of YAP and subsequently downregulated the expression of MMP13 and ADAMTS5. Intra-articular injection of the Piezo1 inhibitor, GsMTx4, could ameliorate proteoglycan degradation in malocclusion-induced TMJOA and suppressed MMP13 and ADAMTS5 expression. CONCLUSIONS: Our results revealed that the activation of Piezo1 promotes mechanical-induced cartilage degradation through the YAP-MMP13/ADAMTS5 signaling pathway.

Augmentation of BMP Signaling in Cranial Neural Crest Cells Leads to Premature Cranial Sutures Fusion through Endochondral Ossification in Mice.

Craniosynostosis is a congenital anomaly characterized by the premature fusion of cranial sutures. Sutures are a critical connective tissue that regulates bone growth; their aberrant fusion results in abnormal shapes of the head and face. The molecular and cellular mechanisms have been investigated for a long time, but knowledge gaps remain between genetic mutations and mechanisms of pathogenesis for craniosynostosis. We previously demonstrated that the augmentation of bone morphogenetic protein (BMP) signaling through constitutively active BMP type 1A receptor (caBmpr1a) in neural crest cells (NCCs) caused the development of premature fusion of the anterior frontal suture, leading to craniosynostosis in mice. In this study, we demonstrated that ectopic cartilage forms in sutures prior to premature fusion in caBmpr1a mice. The ectopic cartilage is subsequently replaced by bone nodules leading to premature fusion with similar but unique fusion patterns between two neural crest-specific transgenic Cre mouse lines, P0-Cre and Wnt1-Cre mice, which coincides with patterns of premature fusion in each line. Histologic and molecular analyses suggest that endochondral ossification in the affected sutures. Both in vitro and in vivo observations suggest a greater chondrogenic capacity and reduced osteogenic capability of neural crest progenitor cells in mutant lines. These results suggest that the augmentation of BMP signaling alters the cell fate of cranial NCCs toward a chondrogenic lineage to prompt endochondral ossification to prematurely fuse cranial sutures. By comparing P0-Cre;caBmpr1a and Wnt1-Cre;caBmpr1a mice at the stage of neural crest formation, we found more cell death of cranial NCCs in P0-Cre;caBmpr1a than Wnt1-Cre;caBmpr1a mice at the developing facial primordia. These findings may provide a platform for understanding why mutations of broadly expressed genes result in the premature fusion of limited sutures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

PEEK for Oral Applications: Recent Advances in Mechanical and Adhesive Properties.

Polyetheretherketone (PEEK) is a thermoplastic material widely used in engineering applications due to its good biomechanical properties and high temperature stability. Compared to traditional metal and ceramic dental materials, PEEK dental implants exhibit less stress shielding, thus better matching the mechanical properties of bone. As a promising medical material, PEEK can be used as implant abutments, removable and fixed prostheses, and maxillofacial prostheses. It can be blended with materials such as fibers and ceramics to improve its mechanical strength for better clinical dental applications. Compared to conventional pressed and CAD/CAM milling fabrication, 3D-printed PEEK exhibits excellent flexural and tensile strength and parameters such as printing temperature and speed can affect its mechanical properties. However, the bioinert nature of PEEK can make adhesive bonding difficult. The bond strength can be improved by roughening or introducing functional groups on the PEEK surface by sandblasting, acid etching, plasma treatment, laser treatment, and adhesive systems. This paper provides a comprehensive overview of the research progress on the mechanical properties of PEEK for dental applications in the context of specific applications, composites, and their preparation processes. In addition, the research on the adhesive properties of PEEK over the past few years is highlighted. Thus, this review aims to build a conceptual and practical toolkit for the study of the mechanical and adhesive properties of PEEK materials. More importantly, it provides a rationale and a general new basis for the application of PEEK in the dental field.

Ferroptosis: The Entanglement between Traditional Drugs and Nanodrugs in Tumor Therapy.

Ferroptosis is a non-apoptotic programmed cell death caused by the accumulation of lipid peroxide. System Xc-/glutathione peroxidase 4 (GPX4) axis and iron axis are two main pathways regulating ferroptosis. Simultaneously, multiple pathways are also involved in the ferroptosis regulation. Ferroptosis is an intense area of the current study. With the improvement of the regulatory mechanisms that underlie ferroptosis, a variety of drugs associated with ferroptosis have been discovered and developed for cancer therapy. Among them, traditional drugs were developed initially. Small molecule compounds that regulate ferroptosis signaling pathway and iron complexes that promote the Fenton reaction have become important drugs for inducing ferroptosis. In recent years, the emerging development of nanotechnology has promoted the research of ferroptosis nanodrugs. Iron-based nanomaterials are extensively tested as ferroptosis-inducing agents. Furthermore, nanoscale drug delivery systems offer a suitable scaffold for traditional drug therapies. Traditional drugs and nanodrugs are complementary, each with their own strengths and limitations. This review describes the latest studies on the regulation of ferroptosis in tumor cells and focuses on the entanglement between traditional drugs and nanodrugs. To conclude, the challenges and perspectives in this field are put forward.

Effect of angiopoietin 4 on odontogenic differentiation of dental pulp stem cells / 口腔疾病防治

Objective @# To investigate the effects of angiopoietin 4 (ANGPT4) on the odontogenic differentiation of human dental pulp stem cells. @* Methods @#This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Human premolars were fixed, decalcified, dehydrated, embedded, and sectioned. Immunofluorescence staining was used to observe the expression and localization of ANGPT4. Human dental pulp stem cells (hDPSCs) were isolated and cultured in vitro. The growth state and morphology of hDPSCs were observed under an inverted phase contrast microscope. The expression of cell surface-related molecular markers was detected by flow cytometry. Alkaline phosphatase and alizarin red S staining were used to detect the odontogenic differentiation potential of hDPSCs. Oil-red O staining was used to detect the adipogenic differentiation potential of hDPSCs. RNA was extracted from hDPSCs at different time points after odontogenic induction, and RT-qPCR was used to analyze the mRNA expression of ANGPT4 and odontogenic-related genes during the odontogenic differentiation of hDPSCs in vitro. siRNA gene silencing technology was used to silence the expression of ANGPT4 in hDPSCs, and the silencing efficiency was detected by RT-qPCR and Western Blot. After silencing ANGPT4 in hDPSCs for 24 h, odontogenic induction was performed. Alkaline phosphatase and alizarin red S staining were performed on the 7th and 14th of induction to detect the odontogenic differentiation ability of hDPSCs after silencing ANGPT4@*Results @# Immunofluorescence staining of human premolars showed that ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone. hDPSCs were in good condition after 14 days of isolation and culture. Under the microscope, multiple cell colonies were observed, and the cell morphology was uniform and long spindle-shaped. The results of flow cytometry showed that hDPSCs expressed mesenchymal stem cell markers CD105 (90.42%) and CD90 (97.15%), but did not express hematopoietic cell markers CD45 (0.01%) and CD34 (0.08%). After odontogenic and adipogenic induction of hDPSCs, alkaline phosphatase staining, alizarin red S staining and oil red O staining were positive. The results of RT-qPCR after the odontogenic induction of hDPSCs showed that ANGPT4 was highly expressed on the 5th, 7th, 11th and 14th days of differentiation of hDPSCs (P<0.05), with the highest expression level on the 5th day. After hDPSCs were transfected with si-ANGPT4, the expression of ANGPT4 mRNA and protein was significantly down-regulated (P<0.05). The results of alkaline phosphatase staining showed that ALP staining intensity and area in the si-ANGPT4 group were significantly lower than those in the negative control. Alizarin red S staining showed that the formation of calcium nodules in the si-ANGPT4 group was significantly lower than that in the negative control.@* Conclusion@#ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone of human premolars. ANGPT4 may be a factor to promote the odontogenic differentiation of hDPSCs.

[Changes of the World Health Organization 2022 classification (5th edition) of salivary glands tumors].

Pathological diagnosis of salivary gland tumors is one of the most challenging areas in all head and neck surgical pathology. The classification of salivary gland tumors was updated in the 5th edition of the World Health Organization Classification of Head and Neck Tumours, most of which were based on their molecular pathological characteristerics. This new classification features a description of several new entitiesamong benign and malignant neoplasms, salivary gland tumors with updated naming or diagnostic criteria, and lesions deleted from this section, etc.This present review focuses on the updates and changes in the new classification of salivary gland tumors, and provides some reference for head and neck surgeons and pathologists.