In order to eliminate the meshing interference between the flexspline and circular spline after the taper deformation of the flexspline,the radial deformation difference method,major and minor axis fitting method,and ...In order to eliminate the meshing interference between the flexspline and circular spline after the taper deformation of the flexspline,the radial deformation difference method,major and minor axis fitting method,and ellipse fitting method are used to modify the tooth thickness of the flexspline and analyze the performance indexes such as the assembly stress,transmission error,and fatigue life.Firstly,the conjugate tooth profile is solved based on the quadruple-circular-arc tooth profile and modified kinematic method.Then,based on the finite element radial deformation of the flexspline,the principle and characteristics of three modification methods are analyzed,and the modification amount of each section of the flexspline tooth is calculated.Finally,the influence of the three modification methods on the performance of the harmonic drive is compared.The results show that the radial deformation difference method can initially determine the modification amount.The minimum static assembly stress is 406.22 MPa by the major and minor axis fitting method.The ellipse fitting method has the best dynamic performance,small transmission error fluctuation,a peak-to-peak value of 3.060",and a maximum fatigue life of 10^(7.558)cycles.展开更多
Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playin...Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.展开更多
The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a d...The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.展开更多
Accurate and early evaluation of dental physiological characteristics is essential for effective disease detection and management.Polarization-sensitive optical coherence tomography(PS-OCT)is a noninvasive high-resolu...Accurate and early evaluation of dental physiological characteristics is essential for effective disease detection and management.Polarization-sensitive optical coherence tomography(PS-OCT)is a noninvasive high-resolution imaging technique that can obtain tooth structure and physiological features through intensity,retardation and degree of polarization uniformity(DOPU)images.In this study,we use the information provided by the PS-OCT system,especially the retardation information,to assess the physiological characteristics of teeth.In addition,we introduce a novel parameter—the rate of change of the retardation value(R)—to evaluate the magnitude of birefringence of enamel,which serves as an indicator of enamel health and mineralization.The results demonstrate that PS-OCT not only provides structural detail comparable to microcomputed tomography(microCT),but also yields additional physiological characteristics insights through polarization-based contrast.These findings highlight the strong potential of PS-OCT for early diagnosis,functional evaluation and personalized monitoring in dental care.展开更多
Mango(Mangifera indica L.)is one of the main economic crops in Hainan,China,prized for its distinctive flavor and high nutritional value.It is also rich in health-promoting antioxidants such as vitamin C and flavonoid...Mango(Mangifera indica L.)is one of the main economic crops in Hainan,China,prized for its distinctive flavor and high nutritional value.It is also rich in health-promoting antioxidants such as vitamin C and flavonoids.Enhanced ultraviolet-B(UV—B)radiation,a growing global environmental concern,alters plant antioxidant systems,with increased flavonoid accumulation as a common adaptive response.However,its effects on mango fruit remain largely unexplored.To investigate the antioxidant responses of mango to enhanced UV-B radiation and identify key responsive flavonoid compounds and regulatory genes,we exposed‘Tainong 1’mango fruits growing under natural light to 96 kJ·m^(-2)·d^(-1)of UV-B radiation to simulate high UV-B conditions.Treated fruits were smaller in size and had a pulp of a more intense yellow colour.Further,malondialdehyde content in treated fruits was higher during the phase of rapid fruit enlargement.Additionally,treated fruits showed increased sugar-acid ratios,total phenol,total flavonoid,carotenoid,and ascorbic acid contents.Furthermore,they showed significantly enhanced antioxidant activity,as measured by the FRAP,ABTS,and DPPH assays.Extensive targeted metabolomic-analysis identified flavonoids as the largest category of compounds differentially expressed in treated and control groups.Quantitative metabolomics of flavonoids identified hyperoside,quercimeritrin,and(-)-catechin gallate as the key flavonoid metabolites responsive to UV-B treatment.Transcriptome analysis revealed an enrichment of the flavonoid biosynthesis pathway,with most associated differentially expressed genes showing upregulation.Furthermore,qRT-PCR analysis confirmed that the expression of the genes MiCHS7,MiCHI1,MiCHI2,MiFLS,MiF3H2,and MiF3H3 correlated with changes in key flavonoid metabolites.Indeed,correlation analysis indicated that MiCHS7,MiCHI1,MiFLS,and MiF3H3 are potential key genes involved in flavonoid accumulation under UV-B treatment.Thus,our study provides a theoretical basis for breeding for new resilient varieties and developing UV-B-resistant mango cultivation techniques.展开更多
Tooth developmental anomalies are a group of disorders caused by unfavorable factors affecting the tooth development process,resulting in abnormalities in tooth number,structure,and morphology.These anomalies typicall...Tooth developmental anomalies are a group of disorders caused by unfavorable factors affecting the tooth development process,resulting in abnormalities in tooth number,structure,and morphology.These anomalies typically manifest during childhood,impairing dental function,maxillofacial development,and facial aesthetics,while also potentially impacting overall physical and mental health.The complex etiology and diverse clinical phenotypes of these anomalies pose significant challenges for prevention,early diagnosis,and treatment.As they usually emerge early in life,long-term management and multidisciplinary collaboration in dental care are essential.However,there is currently a lack of systematic clinical guidelines for the diagnosis and treatment of these conditions,adding to the difficulties in clinical practice.In response to this need,this expert consensus summarizes the classifications,etiology,typical clinical manifestations,and diagnostic criteria of tooth developmental anomalies based on current clinical evidence.It also provides prevention strategies and stage-specific clinical management recommendations to guide clinicians in diagnosis and treatment,promoting early intervention and standardized care for these anomalies.展开更多
The peripheral nerve injuries,representing some of the most common types of traumatic lesions affecting the nervous system,are highly invalidating for the patients besides being a huge social burden.Although periphera...The peripheral nerve injuries,representing some of the most common types of traumatic lesions affecting the nervous system,are highly invalidating for the patients besides being a huge social burden.Although peripheral nervous system owns a higher regenerative capacity than does central nervous system,mostly depending on Schwann cells intervention in injury repair,several factors determine the extent of functional outcome after healing.Based on the injury type,different therapeutic approaches have been investigated so far.Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries,however these approaches own limitations,such as scarce donor nerve availability and donor site morbidity.Cell based therapies might provide a suitable tool for peripheral nerve regeneration,in fact,the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade.Dental pulp is a promising cell source for regenerative medicine,because of the ease of isolation procedures,stem cell proliferation and multipotency abilities,which are due to the embryological origin from neural crest.In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models,highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.展开更多
The ability of human deciduous tooth dental pulp cells（HDDPCs） to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medic...The ability of human deciduous tooth dental pulp cells（HDDPCs） to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medicine. Realization of this potential depends on efficient and optimized protocols for the genetic manipulation of HDDPCs. In this study, we demonstrate the use of a Piggy Bac（PB）-based gene transfer system as a method for introducing nonviral transposon DNA into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection efficiency of the PB-based system was significantly greater than previously reported for electroporation-based transfection of plasmid DNA. Using the neomycin resistance gene as a selection marker, HDDPCs were stably transfected at a rate nearly 40-fold higher than that achieved using conventional methods. Using this system, it was also possible to introduce two constructs simultaneously into a single cell. The resulting stable transfectants, expressing td Tomato and enhanced green fluorescent protein, exhibited both red and green fluorescence. The established cell line did not lose the acquired phenotype over three months of culture. Based on our results, we concluded that PB is superior to currently available methods for introducing plasmid DNA into HDDPCs. There may be significant challenges in the direct clinical application of this method for human dental tissue engineering due to safety risks and ethical concerns. However, the high level of transfection achieved with PB may have significant advantages in basic scientific research for dental tissue engineering applications, such as functional studies of genes and proteins. Furthermore, it is a useful tool for the isolation of genetically engineered HDDPC-derived stem cells for studies in tooth regenerative medicine.展开更多
A method of treating pulpless coloured anterior tooth is presented.Most part ofthe coloured dentin of the labial crown was removed and the dental structure was bleachedwith 30% hydrogen peroxide for 5min.The pulp cavi...A method of treating pulpless coloured anterior tooth is presented.Most part ofthe coloured dentin of the labial crown was removed and the dental structure was bleachedwith 30% hydrogen peroxide for 5min.The pulp cavity was then filled with whitephoto-curing composite.The result of the treatment is quite satisfactory.With our treatment,the intact contour of the crown and the hardness and gloss of the enamel are preserved.SEM proved that the composite was tightly bound with the enamel of the medial wall of thepulp cavity,forming an entity with the tooth,thus guaranteeing the strength of the crown.展开更多
Summary： We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to re- cord ATP-activated current i...Summary： We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to re- cord ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons （F, I and S） were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2Xl and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.展开更多
Introduction: The endodontic management of necrotic permanent immature teeth is a challenge for the practitioner. These teeth are treated by apexification. However, because of the complications associated with this tr...Introduction: The endodontic management of necrotic permanent immature teeth is a challenge for the practitioner. These teeth are treated by apexification. However, because of the complications associated with this treatment, researchers have developed other therapies. Currently, a new technique called pulp revascularization has emerged. This technique allows the continuation of root completion thanks to a healthy tissue newly formed at the intra root canal level. Material and method: A literature search of articles dealing with pulp revascularization of immature permanent teeth was conducted using two types of search strategy, a literature search using keywords on databases and then a manual “bottom-up” search of references of previously identified articles. Results: 112 articles were identified based on inclusion and exclusion criteria. Discussion: This work showed that pulp revascularization is a new therapy that aims to restart root development on an immature permanent tooth. It is based on the principle of tissue engineering and uses the differentiation potential of stem cells. Conclusion: Currently, the literature values revascularization as it allows root development, sidewall thickening, apical closure and a decrease in periapical lesion and ensures a good sealing. Clinical and radiographic success rates appear to be encouraging, except that factors influencing treatment must be taken into consideration.展开更多
In this study, we investigated whether increases in hippocampal blood flow (HBF) by tooth pulp stimulation (TPS) are mediated via the activation of cyclooxygenase-2 (COX-2). We measured mean arterial blood pressure (M...In this study, we investigated whether increases in hippocampal blood flow (HBF) by tooth pulp stimulation (TPS) are mediated via the activation of cyclooxygenase-2 (COX-2). We measured mean arterial blood pressure (MABP) and HBF in urethane-anesthetized rats using laser Doppler flowmetry and examined the effects of etodolac, a specific COX-2 inhibitor, on TPS-induced MABP and HBF responses. The MABP response was not attenuated by the intraperitoneal (i.p.) administration of etodolac (10 mg/kg);however, the HBF response was significantly attenuated by etodolac administration. These results suggest that COX-2 may be involved in the mechanisms regulating TPS-induced HBF responses.展开更多
Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellula...Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B.Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B,thereby regulating tooth development.An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice.In conclusion,this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization,which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.展开更多
Pulpotomy,which belongs to vital pulp therapy,has become a strategy for managing pulpitis in recent decades.This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing l...Pulpotomy,which belongs to vital pulp therapy,has become a strategy for managing pulpitis in recent decades.This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes.Pulpotomy is categorized into partial pulpotomy(PP),the removal of a partial segment of the coronal pulp tissue,and full pulpotomy(FP),the removal of whole coronal pulp,which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth.Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality,the overall treatment plan,the patient’s general health status,and pulp inflammation reassessment during operation.This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics,Chinese Stomatological Association.It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment(RCT)on mature permanent teeth with pulpitis from a biological basis,the development of capping biomaterial,and the diagnostic considerations to evidence-based medicine.This expert statement intends to provide a clinical protocol of pulpotomy,which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.展开更多
Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family memb...Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family member distributed in bones and teeth.It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells(hDPSCs).In this study,the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated.The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining.Intriguingly,the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens.The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide(LPS)-induced inflammation.A conditional Omd knockout mouse model with pulpal inflammation was established.LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice,whereas OMD administration exhibited a protective effect against pulpitis.Mechanistically,the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB(NF-κB)signaling pathway.Interleukin-1 receptor 1(IL1R1),a vital membrane receptor activating the NF-κB pathway,was significantly downregulated in OMD-overexpressing hDPSCs.Additionally,the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking.In vivo,excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist.Overall,OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway.OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.展开更多
Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon(RAP).Despite its therapeutic effects,the surgical risk and unclear mechanism hamper th...Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon(RAP).Despite its therapeutic effects,the surgical risk and unclear mechanism hamper the clinical application.Numerous evidences support macrophages as the key immune cells during bone remodeling.Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1CreERT2;R26GFP lineage tracing system.Fluorescence staining,flow cytometry analysis,and western blot determined the significantly enhanced expression of binding immunoglobulin protein(BiP)and emphasized the activation of sensor activating transcription factor 6(ATF6)in macrophages.Then,we verified that macrophage specific ATF6 deletion(ATF6f/f;CX3CR1CreERT2 mice)decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy.In contrast,macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement.In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6.At the mechanism level,RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfαpromotor and augmenting its transcription.Additionally,molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element(ERSE).Taken together,ATF6 may aggravate orthodontic bone remodeling by promoting Tnfαtranscription in macrophages,suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.展开更多
Spiral bevel gears are critical transmission components,and are widely used in the aerospace field.This paper proposes a new multi-DOF envelope forming process for fabricating spiral bevel gears.Firstly,the multi-DOF ...Spiral bevel gears are critical transmission components,and are widely used in the aerospace field.This paper proposes a new multi-DOF envelope forming process for fabricating spiral bevel gears.Firstly,the multi-DOF envelope forming principle of spiral bevel gears is proposed.Secondly,the design methods for the envelope tool geometry and movement are proposed based on the envelope geometry and movement relationships.Thirdly,the metal flow and tooth filling laws are revealed through 3D FE simulation of the multi-DOF envelope forming process of a typical spiral bevel gear.Fourthly,a new method for separating the envelope tool and the formed spiral bevel gear with back taper tooth is proposed to avoid their interference.Finally,experiments on multi-DOF envelope forming of this typical spiral bevel gear are conducted using new heavy load multi-DOF envelope forming equipment.The simulation and experimental results show the feasibility of the proposed multi-DOF envelope forming process for fabricating spiral bevel gears with back taper tooth and the corresponding process design methods.展开更多
Background: Tooth loss results in impaired mastication, which in turn, makes it difficult to chew hard food, consequently leading to deteriorate dietary habits and to develop hypertension. The purpose of this study wa...Background: Tooth loss results in impaired mastication, which in turn, makes it difficult to chew hard food, consequently leading to deteriorate dietary habits and to develop hypertension. The purpose of this study was to examine the effect of tooth loss on blood pressure among Congolese population. Methods: A cross-sectional study was conducted from October 2019 until December 2023 among Congolese population aged at least 30 years reporting to the living in DR Congo. All participants were enrolled from Dental Clinic located in the DR Congo. To be eligible to participate in the study, were the willing to participate and having signed informed consent;had a missing tooth;had carried out blood pressure measurement (hypertension/normotensive). The exclusion criteria were determined: being less than 30 years old, being pregnant for women considering the risk of existing gestational hypertension, obesity, excessive alcohol consumption, smoking, and diabetes. Hypertension was defined as the mean of three measurements of systolic blood pressure (SBP) (140 mmHg or higher), diastolic blood pressure (DBP) (90 mm or higher) or physician diagnosed hypertension confirmed from medical records. We determined the number of tooth loss from oral examination. A multivariable logistic regression model was used to investigate the effect of tooth loss on blood pressure. Results: In all, 25,396 participants were enrolled among Congolese population for this study. After oral examination, 13,421 were excluded for no tooth loss and 11,975 participants were selected. The average number of tooth loss among study population was 11.06. Among the participants with hypertension had lost an average of 11 teeth, significantly higher than those without hypertension (6.09) (p = 0.001). After adjusting for covariates (socio-demographic characteristics), tooth loss (>10) was significantly associated with hypertension, with OR = 1.32 (95% CI 1.073 - 2.38). Conclusion: Tooth loss maybe associated with severe hypertension among Congolese population adults. Prevention of tooth loss is very important to the overall health of this population.展开更多
Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines.Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies,wh...Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines.Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies,which are incapable of repairing the pulpdentin complex defects.Although biomaterial-based strategies show remarkable progress in antibacterial,anti-inflammatory,and pulp regeneration,the important modulatory effects of nerves within pulp cavity have been greatly overlooked,making it challenging to achieve functional pulp-dentin complex regeneration.In this study,we propose an injectable bioceramicscontaining composite hydrogel in combination of Li-Ca-Si(LCS)bioceramics and gelatin methacrylate matrix with photocrosslinking properties.Due to the sustained release of bioactive Li,Ca and Si ions from LCS,the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells,odontogenic differentiation of dental pulp stem cells,and neurogenesis-odontogenesis couples in vitro.In addition,the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair.More importantly,LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers,leading to the re-innervation of pulp tissues.Taken together,the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair,offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.展开更多
文摘In order to eliminate the meshing interference between the flexspline and circular spline after the taper deformation of the flexspline,the radial deformation difference method,major and minor axis fitting method,and ellipse fitting method are used to modify the tooth thickness of the flexspline and analyze the performance indexes such as the assembly stress,transmission error,and fatigue life.Firstly,the conjugate tooth profile is solved based on the quadruple-circular-arc tooth profile and modified kinematic method.Then,based on the finite element radial deformation of the flexspline,the principle and characteristics of three modification methods are analyzed,and the modification amount of each section of the flexspline tooth is calculated.Finally,the influence of the three modification methods on the performance of the harmonic drive is compared.The results show that the radial deformation difference method can initially determine the modification amount.The minimum static assembly stress is 406.22 MPa by the major and minor axis fitting method.The ellipse fitting method has the best dynamic performance,small transmission error fluctuation,a peak-to-peak value of 3.060",and a maximum fatigue life of 10^(7.558)cycles.
基金supported by the National Key Research and Development Program of China to W.Tian (2022YFA1104400)the National Natural Science Foundation of China to T.Chen (82100959)a grant from the Sichuan Science and Technology Program to Z.Liu (2024YFFK0068)。
文摘Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.
基金supported by the National Natural Science Foundation of China(82170951,82470961)the Beijing Natural Science Foundation (7222079)+4 种基金the Beijing Hospital Authority"Dengfeng"Talent Training Plan (DFL 20221301)the Beijing Stomatological HospitalCapital Medical University Young Scientist Program (No.YSP202401)the Laboratory for Clinical Medicine and the Central Laboratory of Capital Medical University for their technical support and fundingthe Japan China Sasakawa Medical Fellowship for their generous support and funding。
文摘The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.
基金supported by the National Natural Science Foundation of China(Nos.62375144 and 12404345)"the Fundamental Research Funds for the Central Universities",Nankai University(No.63241331).
文摘Accurate and early evaluation of dental physiological characteristics is essential for effective disease detection and management.Polarization-sensitive optical coherence tomography(PS-OCT)is a noninvasive high-resolution imaging technique that can obtain tooth structure and physiological features through intensity,retardation and degree of polarization uniformity(DOPU)images.In this study,we use the information provided by the PS-OCT system,especially the retardation information,to assess the physiological characteristics of teeth.In addition,we introduce a novel parameter—the rate of change of the retardation value(R)—to evaluate the magnitude of birefringence of enamel,which serves as an indicator of enamel health and mineralization.The results demonstrate that PS-OCT not only provides structural detail comparable to microcomputed tomography(microCT),but also yields additional physiological characteristics insights through polarization-based contrast.These findings highlight the strong potential of PS-OCT for early diagnosis,functional evaluation and personalized monitoring in dental care.
基金financially supported by the National Natural Science Foundation of China(Grant No.32160677)the Hainan University Mango Research System.
文摘Mango(Mangifera indica L.)is one of the main economic crops in Hainan,China,prized for its distinctive flavor and high nutritional value.It is also rich in health-promoting antioxidants such as vitamin C and flavonoids.Enhanced ultraviolet-B(UV—B)radiation,a growing global environmental concern,alters plant antioxidant systems,with increased flavonoid accumulation as a common adaptive response.However,its effects on mango fruit remain largely unexplored.To investigate the antioxidant responses of mango to enhanced UV-B radiation and identify key responsive flavonoid compounds and regulatory genes,we exposed‘Tainong 1’mango fruits growing under natural light to 96 kJ·m^(-2)·d^(-1)of UV-B radiation to simulate high UV-B conditions.Treated fruits were smaller in size and had a pulp of a more intense yellow colour.Further,malondialdehyde content in treated fruits was higher during the phase of rapid fruit enlargement.Additionally,treated fruits showed increased sugar-acid ratios,total phenol,total flavonoid,carotenoid,and ascorbic acid contents.Furthermore,they showed significantly enhanced antioxidant activity,as measured by the FRAP,ABTS,and DPPH assays.Extensive targeted metabolomic-analysis identified flavonoids as the largest category of compounds differentially expressed in treated and control groups.Quantitative metabolomics of flavonoids identified hyperoside,quercimeritrin,and(-)-catechin gallate as the key flavonoid metabolites responsive to UV-B treatment.Transcriptome analysis revealed an enrichment of the flavonoid biosynthesis pathway,with most associated differentially expressed genes showing upregulation.Furthermore,qRT-PCR analysis confirmed that the expression of the genes MiCHS7,MiCHI1,MiCHI2,MiFLS,MiF3H2,and MiF3H3 correlated with changes in key flavonoid metabolites.Indeed,correlation analysis indicated that MiCHS7,MiCHI1,MiFLS,and MiF3H3 are potential key genes involved in flavonoid accumulation under UV-B treatment.Thus,our study provides a theoretical basis for breeding for new resilient varieties and developing UV-B-resistant mango cultivation techniques.
基金supported by the grants No.82370912 from the National Natural Science Foundation of ChinaNo.2022020801010499 from the Bureau of Science and Technology of Wuhan,ChinaNo.2042023kf0231 from the Fundamental Research Funds for the Central Universities,China。
文摘Tooth developmental anomalies are a group of disorders caused by unfavorable factors affecting the tooth development process,resulting in abnormalities in tooth number,structure,and morphology.These anomalies typically manifest during childhood,impairing dental function,maxillofacial development,and facial aesthetics,while also potentially impacting overall physical and mental health.The complex etiology and diverse clinical phenotypes of these anomalies pose significant challenges for prevention,early diagnosis,and treatment.As they usually emerge early in life,long-term management and multidisciplinary collaboration in dental care are essential.However,there is currently a lack of systematic clinical guidelines for the diagnosis and treatment of these conditions,adding to the difficulties in clinical practice.In response to this need,this expert consensus summarizes the classifications,etiology,typical clinical manifestations,and diagnostic criteria of tooth developmental anomalies based on current clinical evidence.It also provides prevention strategies and stage-specific clinical management recommendations to guide clinicians in diagnosis and treatment,promoting early intervention and standardized care for these anomalies.
文摘The peripheral nerve injuries,representing some of the most common types of traumatic lesions affecting the nervous system,are highly invalidating for the patients besides being a huge social burden.Although peripheral nervous system owns a higher regenerative capacity than does central nervous system,mostly depending on Schwann cells intervention in injury repair,several factors determine the extent of functional outcome after healing.Based on the injury type,different therapeutic approaches have been investigated so far.Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries,however these approaches own limitations,such as scarce donor nerve availability and donor site morbidity.Cell based therapies might provide a suitable tool for peripheral nerve regeneration,in fact,the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade.Dental pulp is a promising cell source for regenerative medicine,because of the ease of isolation procedures,stem cell proliferation and multipotency abilities,which are due to the embryological origin from neural crest.In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models,highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.
基金supported in part by a Grant-in-Aid for Scientific Research (C) (grant no. 25463192) from the Ministry of Education, Science, Sports, Culture, and Technology of Japan
文摘The ability of human deciduous tooth dental pulp cells（HDDPCs） to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medicine. Realization of this potential depends on efficient and optimized protocols for the genetic manipulation of HDDPCs. In this study, we demonstrate the use of a Piggy Bac（PB）-based gene transfer system as a method for introducing nonviral transposon DNA into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection efficiency of the PB-based system was significantly greater than previously reported for electroporation-based transfection of plasmid DNA. Using the neomycin resistance gene as a selection marker, HDDPCs were stably transfected at a rate nearly 40-fold higher than that achieved using conventional methods. Using this system, it was also possible to introduce two constructs simultaneously into a single cell. The resulting stable transfectants, expressing td Tomato and enhanced green fluorescent protein, exhibited both red and green fluorescence. The established cell line did not lose the acquired phenotype over three months of culture. Based on our results, we concluded that PB is superior to currently available methods for introducing plasmid DNA into HDDPCs. There may be significant challenges in the direct clinical application of this method for human dental tissue engineering due to safety risks and ethical concerns. However, the high level of transfection achieved with PB may have significant advantages in basic scientific research for dental tissue engineering applications, such as functional studies of genes and proteins. Furthermore, it is a useful tool for the isolation of genetically engineered HDDPC-derived stem cells for studies in tooth regenerative medicine.
文摘A method of treating pulpless coloured anterior tooth is presented.Most part ofthe coloured dentin of the labial crown was removed and the dental structure was bleachedwith 30% hydrogen peroxide for 5min.The pulp cavity was then filled with whitephoto-curing composite.The result of the treatment is quite satisfactory.With our treatment,the intact contour of the crown and the hardness and gloss of the enamel are preserved.SEM proved that the composite was tightly bound with the enamel of the medial wall of thepulp cavity,forming an entity with the tooth,thus guaranteeing the strength of the crown.
基金supported by grants from the National Natural Science Foundation of China (No. 30970927)the Natural Science Foundation of Hubei Province, China (No.2008CDA053)the Wuhan Science and Technology Foundation (Nos. 200970634270, 201250499145-27)
文摘Summary： We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to re- cord ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons （F, I and S） were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2Xl and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.
文摘Introduction: The endodontic management of necrotic permanent immature teeth is a challenge for the practitioner. These teeth are treated by apexification. However, because of the complications associated with this treatment, researchers have developed other therapies. Currently, a new technique called pulp revascularization has emerged. This technique allows the continuation of root completion thanks to a healthy tissue newly formed at the intra root canal level. Material and method: A literature search of articles dealing with pulp revascularization of immature permanent teeth was conducted using two types of search strategy, a literature search using keywords on databases and then a manual “bottom-up” search of references of previously identified articles. Results: 112 articles were identified based on inclusion and exclusion criteria. Discussion: This work showed that pulp revascularization is a new therapy that aims to restart root development on an immature permanent tooth. It is based on the principle of tissue engineering and uses the differentiation potential of stem cells. Conclusion: Currently, the literature values revascularization as it allows root development, sidewall thickening, apical closure and a decrease in periapical lesion and ensures a good sealing. Clinical and radiographic success rates appear to be encouraging, except that factors influencing treatment must be taken into consideration.
文摘In this study, we investigated whether increases in hippocampal blood flow (HBF) by tooth pulp stimulation (TPS) are mediated via the activation of cyclooxygenase-2 (COX-2). We measured mean arterial blood pressure (MABP) and HBF in urethane-anesthetized rats using laser Doppler flowmetry and examined the effects of etodolac, a specific COX-2 inhibitor, on TPS-induced MABP and HBF responses. The MABP response was not attenuated by the intraperitoneal (i.p.) administration of etodolac (10 mg/kg);however, the HBF response was significantly attenuated by etodolac administration. These results suggest that COX-2 may be involved in the mechanisms regulating TPS-induced HBF responses.
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
基金supported by the National Natural Science Foundation of China(No.82071078,82370939)the Shaanxi Provincial High-level Talent Program and Young Talent Support Plan of Xi’an Jiaotong University.
文摘Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B.Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B,thereby regulating tooth development.An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice.In conclusion,this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization,which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.
基金supported by the National Natural Science Foundation of China(82170941 and 82370948 to Lu Zhang,82071110 and 82230029 to Zhi Chen)the National Key R&D Program of China(2018YFC1105100)。
文摘Pulpotomy,which belongs to vital pulp therapy,has become a strategy for managing pulpitis in recent decades.This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes.Pulpotomy is categorized into partial pulpotomy(PP),the removal of a partial segment of the coronal pulp tissue,and full pulpotomy(FP),the removal of whole coronal pulp,which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth.Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality,the overall treatment plan,the patient’s general health status,and pulp inflammation reassessment during operation.This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics,Chinese Stomatological Association.It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment(RCT)on mature permanent teeth with pulpitis from a biological basis,the development of capping biomaterial,and the diagnostic considerations to evidence-based medicine.This expert statement intends to provide a clinical protocol of pulpotomy,which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
基金supported by grants from the National Natural Science Foundation of China (82071104)Science and Technology Commission of Shanghai Municipality (23XD1434200/22Y21901000)+9 种基金Shanghai Hospital Development Center(SHDC12022120)National Clinical Research Center for Oral Diseases (NCRCO2021-omics-07)Shanghai Clinical Research Center for Oral Diseases (19MC1910600)Major and Key Cultivation Projects of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZP006)Shanghai’s Top Priority Research Center (2022ZZ01017)CAMS Innovation Fund for Medical Sciences (2019-I2M-5-037)Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(JYZZ237)Eastern Talent Plan Leading Project (BJZH2024001)partly supported by the Shanghai Ninth People’s Hospital affiliated with Shanghai Jiao Tong University,School of Medicine(JYJC202223)Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases (14DZ2260300)
文摘Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family member distributed in bones and teeth.It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells(hDPSCs).In this study,the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated.The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining.Intriguingly,the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens.The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide(LPS)-induced inflammation.A conditional Omd knockout mouse model with pulpal inflammation was established.LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice,whereas OMD administration exhibited a protective effect against pulpitis.Mechanistically,the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB(NF-κB)signaling pathway.Interleukin-1 receptor 1(IL1R1),a vital membrane receptor activating the NF-κB pathway,was significantly downregulated in OMD-overexpressing hDPSCs.Additionally,the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking.In vivo,excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist.Overall,OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway.OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
基金supported by the National Natural Science Foundation of China(82071143,82371000,82270361)Key Research and Development Program of Jiangsu Province(BE2022795)+2 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_1801)the Jiangsu Province Capability Improvement Project through the Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon(RAP).Despite its therapeutic effects,the surgical risk and unclear mechanism hamper the clinical application.Numerous evidences support macrophages as the key immune cells during bone remodeling.Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1CreERT2;R26GFP lineage tracing system.Fluorescence staining,flow cytometry analysis,and western blot determined the significantly enhanced expression of binding immunoglobulin protein(BiP)and emphasized the activation of sensor activating transcription factor 6(ATF6)in macrophages.Then,we verified that macrophage specific ATF6 deletion(ATF6f/f;CX3CR1CreERT2 mice)decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy.In contrast,macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement.In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6.At the mechanism level,RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfαpromotor and augmenting its transcription.Additionally,molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element(ERSE).Taken together,ATF6 may aggravate orthodontic bone remodeling by promoting Tnfαtranscription in macrophages,suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
基金the National Science and Technology Major Project of China(No.2019-VII0017e0158)the National Natural Science Foundation of China(No.U21A20131)+1 种基金the Industry-University Research Cooperation Project,China(No.HFZL2020CXY025)the National Key Laboratory of Science and Technology on Helicopter Transmission,China(No.HTL-O-21G05).
文摘Spiral bevel gears are critical transmission components,and are widely used in the aerospace field.This paper proposes a new multi-DOF envelope forming process for fabricating spiral bevel gears.Firstly,the multi-DOF envelope forming principle of spiral bevel gears is proposed.Secondly,the design methods for the envelope tool geometry and movement are proposed based on the envelope geometry and movement relationships.Thirdly,the metal flow and tooth filling laws are revealed through 3D FE simulation of the multi-DOF envelope forming process of a typical spiral bevel gear.Fourthly,a new method for separating the envelope tool and the formed spiral bevel gear with back taper tooth is proposed to avoid their interference.Finally,experiments on multi-DOF envelope forming of this typical spiral bevel gear are conducted using new heavy load multi-DOF envelope forming equipment.The simulation and experimental results show the feasibility of the proposed multi-DOF envelope forming process for fabricating spiral bevel gears with back taper tooth and the corresponding process design methods.
文摘Background: Tooth loss results in impaired mastication, which in turn, makes it difficult to chew hard food, consequently leading to deteriorate dietary habits and to develop hypertension. The purpose of this study was to examine the effect of tooth loss on blood pressure among Congolese population. Methods: A cross-sectional study was conducted from October 2019 until December 2023 among Congolese population aged at least 30 years reporting to the living in DR Congo. All participants were enrolled from Dental Clinic located in the DR Congo. To be eligible to participate in the study, were the willing to participate and having signed informed consent;had a missing tooth;had carried out blood pressure measurement (hypertension/normotensive). The exclusion criteria were determined: being less than 30 years old, being pregnant for women considering the risk of existing gestational hypertension, obesity, excessive alcohol consumption, smoking, and diabetes. Hypertension was defined as the mean of three measurements of systolic blood pressure (SBP) (140 mmHg or higher), diastolic blood pressure (DBP) (90 mm or higher) or physician diagnosed hypertension confirmed from medical records. We determined the number of tooth loss from oral examination. A multivariable logistic regression model was used to investigate the effect of tooth loss on blood pressure. Results: In all, 25,396 participants were enrolled among Congolese population for this study. After oral examination, 13,421 were excluded for no tooth loss and 11,975 participants were selected. The average number of tooth loss among study population was 11.06. Among the participants with hypertension had lost an average of 11 teeth, significantly higher than those without hypertension (6.09) (p = 0.001). After adjusting for covariates (socio-demographic characteristics), tooth loss (>10) was significantly associated with hypertension, with OR = 1.32 (95% CI 1.073 - 2.38). Conclusion: Tooth loss maybe associated with severe hypertension among Congolese population adults. Prevention of tooth loss is very important to the overall health of this population.
基金funded by the National Key R&D Program of China(2022YFC2405904)the National Natural Science Foundation of China(52272284,32225028)+1 种基金Joint Research Unit Plan of the Chinese Academy of Sciences(121631ZYLH20240014)the Science and Technology Commission of Shanghai Municipality(24520750100)。
文摘Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines.Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies,which are incapable of repairing the pulpdentin complex defects.Although biomaterial-based strategies show remarkable progress in antibacterial,anti-inflammatory,and pulp regeneration,the important modulatory effects of nerves within pulp cavity have been greatly overlooked,making it challenging to achieve functional pulp-dentin complex regeneration.In this study,we propose an injectable bioceramicscontaining composite hydrogel in combination of Li-Ca-Si(LCS)bioceramics and gelatin methacrylate matrix with photocrosslinking properties.Due to the sustained release of bioactive Li,Ca and Si ions from LCS,the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells,odontogenic differentiation of dental pulp stem cells,and neurogenesis-odontogenesis couples in vitro.In addition,the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair.More importantly,LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers,leading to the re-innervation of pulp tissues.Taken together,the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair,offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.
