Pediatric dental diseases, notably dental caries, malocclusion, and dental trauma, remain a significant public health challenge in China, exerting considerable impact on children's oral and general health. Despite growing societal demand for pediatric dental care, China faces a critical shortage and uneven geographic distribution of pediatric dentists, alongside persistent urban-rural disparities in access to oral health services. These challenges underscore the urgent need for educational reforms, workforce policy adjustments, and assessment of the strengths and limitations of recent training initiatives to enhance pediatric dental service delivery. This narrative review aims to: (I) describe the current structure of pediatric dental education in China and recent reforms, notably the integration of degree education with standardized residency training; (II) summarize the epidemiological burden of dental diseases among Chinese children, together with contributing social and geographic factors; (III) outline national policy initiatives targeting children's oral health and existing gaps in implementation; and (IV) discuss innovations in dental education, including student-centered pedagogies and humanities integration. This review provides a comprehensive overview of pediatric dentistry in China and offers strategic recommendations to strengthen workforce training, expand service access, and reduce the burden of pediatric oral diseases.
Aim or purpose: Imbalance of microbiota, inflammation, and tissue destruction are hallmark manifestations of disrupted homeostasis in periodontitis. Restoring homeostasis is critical to avert the advancement of periodontitis. While probiotics exhibit promise in periodontitis treatment, their reliance on long-term oral intake limits the efficancy. This study develops an innovative probiotic bio-heterojunction (Probio-HJ) that integrates Ca2+, black phosphorus nanosheets (BPNS) and Lactobacillus rhamnosus (LGG) to rapidly reestablish periodontal homeostasis. Materials and methods: Probio-HJ was constructed by electrostatic adsorption. Structural characterization (SEM, TEM, AFM, XRD, XPS, UV-vis) confirmed heterojunction formation, while photothermal, photodynamic, and photoelectric properties were assessed. After evaluations of the antibacterial efficacy and biocompatibility in vitro, a rat periodontitis model was established to evaluate the effects on the periodontal microbiota, local inflammation, and alveolar bone loss. RNA sequencing investigated the mechanisms of alveolar bone remodeling. Results: LGG and BPNS successfully formed a heterojunction-like structure. Under near-infrared (NIR) irradiation, Probio-HJ gradually heated up to 45 °C and generated abundant ROS and photocurrent, which effectively killed periodontal pathogens. Without NIR, it scavenged excess free radicals, ensuring biocompatibility and alleviating inflammation. Additionally, it improved the microbiota structure and reduced alveolar bone loss in the rat periodontitis model after 14 days of treatment. RNA sequencing revealed that Probio-HJ inhibits osteoclast differentiation of macrophages under inflammatory conditions through the PPP3CC/NFATc1 pathway. Conclusions: This study proposes a novel method for constructing living bio-heterojunctions and demonstrates their efficacy in rapidly and effectively restoring periodontal homeostasis in periodontitis, presenting a fresh therapeutic approach for periodontitis.
Developing hydrogel dressings with the capabilities to accommodate irregular wounds and provide a cascade disinfective-regenerative microenvironment for wound repair is of great importance to combating pathogenic bacteria-infected wounds but remains an ongoing challenge. To address the conundrum, we devise a molybdoenzymes-emulating bio-heterojunction (M-bioHJ) doped double network (DN) hydrogel dressing for bacterial-infected wound healing. The near-infrared (NIR) photothermal effect of the M-bioHJ facilitates the exchange of multiple dynamic crosslinking sites in the hydrogel, endowing the hydrogel with photo-remote reprocessing capabilities to completely accommodate the encountered irregular wounds and ultimately accomplish the admirable therapeutic effect. Meanwhile, the introduced M-bioHJ shows NIR light-enhanced photodynamic activity to induce a massive engendering of reactive oxygen species (ROS), allowing rapid sterilization without reliance on exogenous hydrogen peroxide. Furthermore, the Mo ions released from the M-bioHJ-encapsulated hydrogel can play a crucial role in reprogramming the macrophage phenotype and determining tissue regeneration. Both in vitro and in vivo evidences authenticate the accelerated healing potential of infected wounds through the synergistic effects of photo-reprocessing, disinfection, and macrophage-reprogramming facilitated by the hydrogel. These findings highlight the promising application prospects of such neoteric M-bioHJ-encapsulated hydrogel dressings for wound disinfection and tissue regeneration.
The periodontal tissue regeneration strategy based on guided tissue regeneration (GTR) membranes is an effective therapy for periodontal defects. Traditional GTR membranes, however, primarily serve as physical barriers and lack antimicrobial and osteogenic functions. Herein, we developed a multifunctional nanofiber membrane with zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded in a hydrophilic gelatin layer. The release of Zn2+ from the ZIF-8 NPs effectively promoted bone tissue repair and simultaneously enabled GTR membranes with >99 antibacterial efficacies against Escherichia coli and Staphylococcus aureus. Additionally, the incorporation of gelatin enhances cellular adhesion and growth. Furthermore, in vivo studies revealed significant bone regeneration, with increased trabecular number and reduced separation. Owing to its multiple functions, excellent biocompatibility and desirable mechanical properties, this membrane has considerable potential in the field of periodontal therapy.
Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.
Deferred diabetic skin healing is an ever-growing complication owing to the hyperglycemic microenvironment, which accelerates the generation of advanced glycated end products (AGEs) and provides a hotbed for pathogenic infection. Here, the H2S-evolving bio-heterojunction enzyme (BioHJzyme), which is consisted by MXene/FeS2 and glucose oxidase (GOx) is devised. It presents glutathione peroxidase (GPx)- and peroxidase (POD)-mimetic antibacterial activity for anti-pathogens and wound regeneration by AGEs depression. The GOx catalyzes glucose, resulting in reducing the bacterial nutrient and supplying H2O2. The POD-mimetic activity of the BioHJzyme catalyzes the H2O2 to hydroxyl radical (center dot OH) with a turnover number of 4.45 x 10(-1) s(-1), while the GPx-mimetic activity of it consumes glutathione for further center dot OH accumulation. The anti-pathogens can be enhanced by near infrared laser (NIR) irradiation owing to the efficient separation of electron-hole pairs originated from the heterostructure, which presents NIR-activatable center dot OH and O-1(2) production. Moreover, the BioHJzyme evolves H2S in acidic environment, acting as an H2S donor, which protects cells around the wound from oxidative damage and AGEs, rescues mitochondrial respiration, improves the extracellular matrix deposition and ameliorates dysfunction of fibroblasts for diabetic skin regeneration through TGF-beta/Smad pathway. The work provides a proof-of-concept for bacteria-invaded diabetic wound regeneration via H2S-evolving BioHJzyme.
γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.
Persistent activation of NLRP3 inflammasomes in infectious diabetic wounds lead to uncontrolled inflammation. Hydrogen sulfide (H2S) gas therapy shows promise in inhibiting inflammasomes. However, on-demand delivery of H2S is challenging, as its biological characteristics are Janus-faced. Herein, we present the anti-inflammasome bio-heterojunction (AI-bioHJ), comprising FeS, Cu2O, and glucose oxidase (GOx), capable of H2S gas evolution and in situ self-transformation to accelerate diabetic wound healing. In this system, AI-bioHJ release H2S to inhibit NLRP3 inflammasomes and recycle excess H2S through a reaction between Cu2O and H2S, maintaining a low H2S concentration while upgrading type I FeS/Cu2O to Z-scheme FeS/CuS bioHJ, and markedly enhancing phototherapy. Additionally, GOx depletes local glucose to generate H2O2, promoting Fenton-like reactions and rapid pathogenic elimination. In vivo and in vitro assessments confirm AI-bioHJ effectively eliminate pathogen, inhibit inflammasomes and facilitate diabetic wound healing. Transcriptome analysis indicates that the FoxO-autophagy axis may mediate the anti-inflammasome effects. Altogether, our work provides enlightenments into programmed H2S-releasing bioHJ for remedying diabetic wounds.
Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe2 O3 , Ti3 C2 -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe2 O3 /Ti3 C2 -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe2+ /Fe3+ into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe2+ overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe2+ into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.
Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.
Treatments for malignant bone tumors are urgently needed to be developed due to the dilemma of precise resection of tumor tissue and subsequent bone defects. Although polyether-ether-ketone (PEEK) has widely attracted attention in the orthopedic field, its bioinertness and poor osteogenic properties significantly restrict its applications in bone tumor treatment. To tackle the daunting issue, we use a hydrothermal technique to fabricate novel PEEK scaffolds modified with molybdenum disulfide (MoS2) nanosheets and hydroxyapatite (HA) nanoparticles. Our dual-effect synergistic PEEK scaffolds exhibit perfect photothermal therapeutic (PTT) property dependent on molybdous ion (Mo2+) concentration and laser power density, superior to conventional PEEK scaffolds. Under near-infrared (NIR) irradiation, the viability of MG63 osteosarcoma cells is significantly reduced by modified PEEK scaffolds, indicating a tumor-killing potential in vitro. Furthermore, the incorporation of HA nanoparticles on the surface of PEEK bolsters proliferation and adherence of MC3T3-E1 cells, boosting mineralization for further bone defect repair. The results of micro-computed tomography (micro-CT) and histological analysis of 4-week treated rat femora demonstrate the preeminent photothermal and osteogenesis capacity of 3D-printed modified scaffolds in vivo. In conclusion, the dual-effect synergistic orthopedic implant with photothermal anticancer property and osteogenic induction activity strikes a balance between tumor treatment and bone development promotion, offering a promising future therapeutic option.
Bromodomain (BD) is an evolutionarily conserved protein module found in 46 different BD-containing proteins (BCPs). BD acts as a specific reader for acetylated lysine residues (KAc) and serves an essential role in transcriptional regulation, chromatin remodeling, DNA damage repair, and cell proliferation. On the other hand, BCPs have been shown to be involved in the pathogenesis of a variety of diseases, including cancers, inflammation, cardiovascular diseases, and viral infections. Over the past decade, researchers have brought new therapeutic strategies to relevant diseases by inhibiting the activity or downregulating the expression of BCPs to interfere with the transcription of pathogenic genes. An increasing number of potent inhibitors and degraders of BCPs have been developed, some of which are already in clinical trials. In this paper, we provide a comprehensive review of recent advances in the study of drugs that inhibit or down-regulate BCPs, focusing on the development history, molecular structure, biological activity, interaction with BCPs and therapeutic potentials of these drugs. In addition, we discuss current challenges, issues to be addressed and future research directions for the development of BCPs inhibitors. Lessons learned from the successful or unsuccessful development experiences of these inhibitors or degraders will facilitate the further development of efficient, selective and less toxic inhibitors of BCPs and eventually achieve drug application in the clinic.
Despite the remarkable progress in ultrastrong mechanical laminate materials, the simultaneous achievement of toughness, stretchability and self-healing properties in biomimetic layered nanocomposites remains a great challenge due to the intrinsic limitations of their hard essences and lack of effective stress transfer at the organic-inorganic fragile boundary. Here, an ultratough nanocomposite laminate is prepared by constructing chain-sliding cross-linking at the interface between sulfonated graphene nanosheets and polyurethane layers based on the ring molecules sliding on the linear polymer chains to release stresses. Unlike traditional supramolecular bonding toughening with limited sliding spacing, our strategy enables interfacial molecular chains reversible slippage when the inorganic nanosheets bear stretching force, providing sufficient interlayer spatial distance for relative sliding to dissipate more energy. The resulting laminates exhibit strong strength (22.33 MPa), supertoughness (219.08 MJ m(-3)), ultrahigh stretchability (>1900 %) and self-healing ability (99.7 %), which far surpass most of reported synthetic and natural laminate materials. Moreover, the fabricated proof-of-concept electronic skin shows excellent flexibility, sensitivity and healability for human physiological signals monitoring. This strategy breaks through the challenge that traditional layered nanocomposites are intrinsically stiff and opens up the functional application of layered nanocomposites in flexible devices.
In virtue of the advantages, such as aesthetics, designability, convenient removal, and comfortable experience, invisible orthodontics (IO) have been widely recognized and accepted by the public. However, most of the membranes currently used for IO only meet the requirement of shape retention. Other vital functions, like antibacterial and antifouling activities, are neglected. Herein, antibacterial composite membranes (ACMs) containing polypropylene (PP), thermoplastic polyurethane (TPU) and poly (hexamethylene guanidine) hydrochloride-sodium stearate (PHMG-SS) were facilely manufactured through the hot-pressing membrane forming technology. ACMs were conferred with favorable transparency (∼70% in the visible light range) and excellent antibacterial ability. Experiment results demonstrated that bactericidal rates of ACMs against Staphylococcus aureus, Escherichia coli and Streptococcus mutans were larger than 99.99%. Noticeably, the amount of protein adhered on the surface of ACMs was only 28.1 μg/cm2, showing ideal antifouling performance. Collectively, the mutifunctional ACMs in the study are expected to be prominent alternatives for existing IO.
The mandibular buccal region spans from the distal side of the mandibular canine to the distal side of the mandibular second molar and is continuous with the retromolar region and the mandibular ramus region. In this anatomical region, two continuous and overlapped sites are clinically available for the placement of mini-implants, i.e. interradicular sites and buccal shelf. The mandibular buccal region is frequently used for the insertion of orthodontic temporary anchorage devices for different orthodontic purposes. Mini-implants inserted at the mandibular buccal region are often clinically applied for a variety of orthodontic indications, e.g. anchorage reinforcement, traction of impacted molars, molar distalisation and molar intrusion. This chapter highlights anatomical characteristics, selection of insertion sites, detailed clinical insertion techniques and clinical applications of mini-implants in the mandibular buccal region.
Strategic bone grafts are required to regenerate periodontal bone defects owing to limited self-healing. Current bioceramic particle or deproteinized bovine bone (DBB) products are not able to ideally meet clinical requirements, such as insufficient operability and slow degradation rates. Herein, a strong-interacted bone graft was designed and synthesized by modifying hydroxyapatite (HA) with a lactide-caprolactone copolymer (PLCL) to improve component homogeneity and mechanical properties. The physical-chemical analysis indicated that HA particles were homogenously distributed in HA/PLCL bone grafts, possessed outstanding thermoplasticity, and facilitated clinic operability and initial mechanical support. The in vitro study suggested that HA/PLCL bone graft degraded in a spatiotemporal model. Micropores were formed on the non-porous surface at the beginning, and interconnected porous structures were gradually generated. Furthermore, HA/PLCL bone grafts exhibited excellent biocompatibility and osteogenic ability as revealed in vitro cell culture and in vivo animal experiments. When applied to rat periodontal bone defects, the HA/PLCL bone graft showed a non-inferior bone regeneration compared to the commercial DBB. This study proposes a potential bone graft for periodontal bone repair with thermoplastic, spatiotemporal degraded, and osteogenic characteristics.
In infectious ischemic wounds, a lack of blood perfusion significantly worsens microbe‐associated infection symptoms and frequently complicates healing. To overcome this daunting issue, antibacterial and angiogenic (2A) bio‐heterojunctions (bio‐HJs) consisting of CuS/MXene heterojunctions and a vascular endothelial growth factor (VEGF)‐mimicking peptide (VMP) are devised and developed to accelerate infectious cutaneous regeneration by boosting angiogenesis via an endogenous–exogenous bistimulatory (EEB) strategy. Assisted by near‐infrared irradiation, the bio‐HJ platform exhibits versatile synergistic photothermal, photodynamic, and chemodynamic effects for robust antibacterial efficacy. In addition, copper ions liberated from 2A bio‐HJs elevate VEGF secretion from fibroblasts, which provokes VEGF receptors (VEGFR) activation through an endogenous pathway, whereas VMP itself promotes an exogenous pathway to facilitate endothelial cell multiplication and tube formation by directly activating the VEGFR signaling pathway. Moreover, employing an in vivo model of infectious ischemic wounds, it is confirmed that the EEB strategy can considerably boost cutaneous regeneration through pathogen elimination, angiogenesis promotion, and collagen deposition. As envisaged, this work leads to the development of a powerful 2A bio‐HJ platform that can serve as an effective remedy for bacterial invasion‐induced ischemic wounds through the EEB strategy.
Hyperglycemic microenvironment in diabetes mellitus inevitably stalls the normal orchestrated course of bone regeneration and encourages pathogenic multiplication. Photodynamic therapy (PDT) and chemo‐dynamic therapy (CDT) are extensively harnessed to combat pathogens, yet deep‐seated diabetic bone defect has difficulty in supplying sufficient oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) stocks, resulting in inferior therapeutic efficiency. To address the tough plaguing, the self‐tandem bio‐heterojunctions (bio‐HJs) consisting of molybdenum disulfide (MoS 2 ), graphene oxide (GO), and glucose oxidase (GOx) are constructed on orthopedic polyetheretherketone (PEEK) implants (SP‐Mo/G@GOx) for amplified chemo‐photodynamic anti‐pathogenic therapy and boosted osseointegration in the deep‐seated diabetic micromilieu. In this system, GOx exhausts glucose to generate H 2 O 2 , which provides an abundant stock for CDT. Besides, the bio‐HJs produce hyperthermia upon near‐infrared light (NIR) to accelerate the dynamic process, which amplifies the antibacterial potency of PDT by promoting the vast yield of singlet oxygen ( 1 O 2 ) in a self‐tandem manner. More importantly, in vivo and in vitro assays demonstrate that the engineered implants exert a captivated bactericidal ability and significantly boost osseointegration in an infectious diabetic bone defect model. As envisaged, this study furnishes a novel tactic to arm orthopedic implants with self‐tandem capability for the remedy of infectious diabetic bone defects.
错殆畸形是指异常咬合关系或错乱颅面结构,是遗传、环境等因素引起的牙齿、颅面以及颌骨畸形[1].错(牙合)畸形会对患者产生多重影响,不仅可以影响口腔健康,颅颌面发育,口面部肌功能,还会进一步影响容貌外观导致社交障碍[2].其发病率自古以来居高不下[3].