Implantable hydrogel-based bioelectronics(IHB)can precisely monitor human health and diagnose diseases.However,achieving biodegradability,biocompatibility,and high conformality with soft tissues poses significant chal...Implantable hydrogel-based bioelectronics(IHB)can precisely monitor human health and diagnose diseases.However,achieving biodegradability,biocompatibility,and high conformality with soft tissues poses significant challenges for IHB.Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues.This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film(GCF)with mechanical programmability.The regulation of GCF nearly covers soft tissue mechanics,an elastic modulus from 20 to 420 kPa,and a Poisson’s ratio from-0.25 to 0.52.The negative Poisson’s ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces.The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability.Notably,the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration.The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.展开更多
Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is ...Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.展开更多
Large bone defect regeneration has always been recognized as a challenging clinical problem due to the difficulty of revascularization.Conventional treatments exhibit certain inherent disadvantages(e.g.,secondary inju...Large bone defect regeneration has always been recognized as a challenging clinical problem due to the difficulty of revascularization.Conventional treatments exhibit certain inherent disadvantages(e.g.,secondary injury,immunization,and potential infections).However,three-dimensional(3D)printing technology as an emerging field can serve as an effective approach to achieve satisfactory revascularization while making up for the above limitations.A wide variety of methods can be used to facilitate blood supply during the design of a 3D-printed scaffold.Importantly,the scaffold structure lays a foundation for the entire printing object;any method to promote angiogenesis can be effective only if it is based on well-designed scaffolds.In this review,different designs related to angiogenesis are summarized by collecting the literature from recent years.The 3D-printed scaffolds are classified into four major categories and discussed in detail,from elementary porous scaffolds to the most advanced bone-like scaffolds.Finally,structural design suggestions to achieve rapid angiogenesis are proposed by analyzing the above architectures.This review can provide a reference for organizations or individual academics to achieve improved bone defect repair and regeneration using 3D printing.展开更多
Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel st...Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel strategy combining benidipine,an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects.Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety.The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus.After internalization into cells,the nanosystem is degraded by lysosomes,and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine,silicon and magnesium ions.Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts,indicating that it might be a potential approach in guiding bone repair in clinical applications.展开更多
Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years.Humanβ-defensin 3,a broad-spectrum antimicrobial peptide has been proven to have a variet...Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years.Humanβ-defensin 3,a broad-spectrum antimicrobial peptide has been proven to have a variety of biological functions in periodontitis;however,relatively few reports have addressed the effects of human periodontal ligament cells(h PDLCs)on osteogenic differentiation.In this study,we evaluated the osteogenic effects of h PDLCs with an adenoviral vector encoding humanβ-defensin 3 in an inflammatory microenvironment.Then humanβ-defensin 3 gene-modified rat periodontal ligament cells were transplanted into rats with experimental periodontitis to observe their effects on periodontal bone repair.We found that the humanβ-defensin 3 gene-modified h PDLCs presented with high levels of osteogenesis-related gene expression and calcium deposition.Furthermore,the p38 MAPK pathway was activated in this process.In vivo,humanβ-defensin 3 gene-transfected rat PDLCs promoted bone repair in SD rats with periodontitis,and the p38 mitogen-activated protein kinase(MAPK)pathway might also have been involved.These findings demonstrate that humanβ-defensin 3 accelerates osteogenesis and that humanβ-defensin 3 gene modification may offer a potential approach to promote bone repair in patients with periodontitis.展开更多
BACKGROUND Several previous studies have reported an unusual root formation in which a fractured apical fragment of an immature root continued to develop independent of the main root after trauma to an immature tooth....BACKGROUND Several previous studies have reported an unusual root formation in which a fractured apical fragment of an immature root continued to develop independent of the main root after trauma to an immature tooth.To date,there have been only rare reports of the continuing apical formation of the fractured root associated with dens evaginatus(DE).This paper presents a case of a separated root tip formation associated with a fractured tubercle of DE.CASE SUMMARY An 11-year-old boy was referred for gingival sinus on the buccal side of the right mandibular second premolar(tooth#45).Clinically,tooth#45 was free of caries,but there was a sign of a fractured tubercle of DE on the occlusal surface.Radiography showed that the root canal of tooth#45 was widely radiolucent.A separated root apex was found apically under the main root and was nearly completely formed with an apical orifice at the apical tip.Tooth#45 was diagnosed as tubular fracture of DE with chronic apical periodontitis.A revascularization technique was recommended to treat the tooth.At 3-mo and 1-yr follow-up,the patient remained asymptomatic.Periapical radiography revealed that the separated root tip distally drifted with closure of the apex.However,the root length and thickness of the main root did not increased.CONCLUSION Clinicians should be aware that even if tubercle of DE is fractured in an immature tooth,the root tip may be separated from the main root and completely formed.展开更多
BACKGROUND Transduodenal local excision is an alternative treatment approach for benign ampullary tumors.However,this procedure has technical difficulties,especially during reconstruction of the pancreaticobiliary duc...BACKGROUND Transduodenal local excision is an alternative treatment approach for benign ampullary tumors.However,this procedure has technical difficulties,especially during reconstruction of the pancreaticobiliary ducts.An operating microscope has been widely used by surgeons for delicate surgery due to its major advantages of magnification,illumination,and stereoscopic view.The application of an operating microscope in transduodenal excision of ampullary tumors has not been reported.CASE SUMMARY A 55-year-old woman was admitted for investigation of recurrent upper abdominal pain.Physical examination and laboratory tests found no abnormalities.Imaging identified a large mass in the descending part of the duodenum.Esophagogastroduodenoscopy revealed a 3.5-cm-sized villous growth over the major duodenal papilla.Pathology of the endoscopic biopsy indicated a villous adenoma with low-grade dysplasia.Microscopic transduodenal excision of the ampullary tumor was performed.The final pathological diagnosis was villous-tubular adenoma with low-grade dysplasia.The patient was discharged on postoperative day 12 after an uneventful recovery.Endoscopic retrograde cholangiopancreatography was performed 3 mo postoperatively and showed no bile duct or pancreatic duct strictures and no tumor recurrence.The patient is continuing follow-up at our clinic and remains well.CONCLUSION Operating microscope-assisted transduodenal local excision is a feasible and effective option for benign ampullary tumors.展开更多
The organized alignment of cells in various tissues plays a significant role in the maintenance of specific functions.To induce such an alignment,ideal scaffolds should simulate the characteristics and morphologies of...The organized alignment of cells in various tissues plays a significant role in the maintenance of specific functions.To induce such an alignment,ideal scaffolds should simulate the characteristics and morphologies of natural tissues.Aligned structures that guide cell orientation are used to facilitate tissue regeneration and repair.We here review how various aligned structures are fabricated,including aligned electrospun nanofibers,aligned porous or channeled structures,micropatterns and combinations thereof,and their application in nerve,skeletal muscle,tendon,and tubular dentin regeneration.The future use of aligned structures in tissue engineering is also discussed.展开更多
Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal,but the details of these mechanisms remain unknown.Here,we investigated t...Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal,but the details of these mechanisms remain unknown.Here,we investigated the expression patterns of a transcription factor,Krüppel-like factor 6(KLF6),during the development of murine tooth germ and its function in odontoblastic differentiation.KLF6 was almost ubiquitously expressed in odontoblasts at various stages,and it was co-expressed with P21(to varying degrees)in mouse dental germ.To determine the function of Klf6,overexpression and knockdown experiments were performed in a mouse dental papilla cell line(iMDP-3).Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of i MDP-3 through p21 upregulation.Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription.Additionally,the in vivo study showed that KLF6 and P21were also co-expressed in odontoblasts around the reparative dentin.In conclusion,Klf6 regulates the transcriptional activity of p21,thus promoting the cell proliferation to odontoblastic differentiation transition in vitro.This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.展开更多
Considering the substantial role played by dendritic cells(DCs) in the immune system to bridge innate and adaptive immunity,studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effe...Considering the substantial role played by dendritic cells(DCs) in the immune system to bridge innate and adaptive immunity,studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces,their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns(BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins(HSPs) and high mobility group box 1(HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.展开更多
The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy efficacy.However,few studies have explored exhausted T cell subpopulations in human cancers.In the present stu...The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy efficacy.However,few studies have explored exhausted T cell subpopulations in human cancers.In the present study,we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer(HNSCC)by multiplex immunohistochemistry(mIHC)to investigate two subsets of Tex,CD8+PD1+TCF1+progenitor exhausted T cells(TCF1+Texprog)and CD8+PD1+TCF1−terminally exhausted T cells(TCF1−Texterm).Moreover,fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells(Tregs)in the tumor immune microenvironment(TIME).mIHC and flow cytometry analysis showed that TCF1−Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients.TCF1+Texprog produced abundant TNFα,while TCF1−Texterm expressed higher levels of CD103,TIM-3,CTLA-4,and TIGIT.TCF1−Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+phenotype;and were associated with better overall survival and recurrence-free survival.The results also indicated that larger proportions of TCF1−Texterm were accompanied by an increase in the proportion of Tregs.Therefore,it was concluded that TCF1−Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival.A high proportion of TCF1−Texterm was associated with greater Treg abundance.展开更多
Research in stomatology(dental medicine)continues to expand globally and is oriented towards solving clinical issues,focusing on clarifying the clinical relevance and potential mechanisms of oral–systemic connections...Research in stomatology(dental medicine)continues to expand globally and is oriented towards solving clinical issues,focusing on clarifying the clinical relevance and potential mechanisms of oral–systemic connections via clinical epidemiology,oral microecological characterization,and the establishment of animal models.Interdisciplinary integration of materials science and tissue engineering with stomatology is expected to lead to the creation of innovative materials and technologies to better resolve the most prevalent and challenging clinical issues such as peri-implantitis,soft and hard tissue defects,and dentin hypersensitivity.With the rapid development of artificial intelligence(AI),5th generation mobile communication technology(5G),and big data applications,“intelligent stomatology”is emerging to build models for better clinical diagnosis and management,accelerate the reform of education,and support the growth and advancement of scientific research.Here,we summarized the current research status,and listed the future prospects and limitations of these three aspects,aiming to provide a basis for more accurate etiological exploration,novel treatment methods,and abundant big data analysis in stomatology to promote the translation of research achievements into practical applications for both clinicians and the public.展开更多
Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanos...Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel.Collectively,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.展开更多
Oral squamous cell carcinoma(OSCC)is one of the most common cancers worldwide,and with 354864 new cases each year.Cancer metastasis,recurrence,and drug resistance are the main causes to cripples and deaths of OSCC pat...Oral squamous cell carcinoma(OSCC)is one of the most common cancers worldwide,and with 354864 new cases each year.Cancer metastasis,recurrence,and drug resistance are the main causes to cripples and deaths of OSCC patients.As potent growth factors,fibroblast growth factors(FGFs)are frequently susceptible to being hijacked by cancer cells.In this study,we show that FGF8 is upregulated in OSCC tissues and high FGF8 expression is related with a set of clinicopathologic parameters,including age,drinking,and survival time.FGF8 treatment enhances the invasive capability of OSCC cells.Lentivirus-based FGF8 expression promotes OSCC metastasis in a mouse lung metastasis model.Further,mechanistic study demonstrates that FGF8 induces epithelial–mesenchymal transition(EMT)in OSCC cells.These results highlight a pro-metastatic function of FGF8,and underscore the role of FGF8 in OSCC development.展开更多
Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems.The heterogeneity of the osteoimmune microenvironment in the osseointegratio...Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems.The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive.Here,a single-cell study involving 40043 cells is conducted,and a total of 10 distinct cell clusters are identified from five different groups.A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties.The increased immature neutrophils,Ly6C+CCR2hi monocytes,and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant.The enrichment of mature neutrophils,FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response.Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration.Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis.These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of‘osteoimmune-smart’biomaterials in the bone regeneration field.展开更多
This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation.Therefore,we chose the chicken myeloid ge...This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation.Therefore,we chose the chicken myeloid gene,mitochondrial import protein 1(mim-1),as a target to study the binding specificity between potential dual-Myb-binding sites.The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT,which contains two AACNG consensuses.Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand(complex F)is more stable than that in the reverse strand(complex R).The principal component analysis(PCA)dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3(R2R3),resulting in the dissociation of DNA from c-Myb in complex R at 330 K,triggered by the reduced electrostatic potential on the surface of R2R3.Furthermore,the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R,which affected on the hydrogenbond formation ability between R2R3 and DNA,and directly resulted in the dissociation of DNA from R2R3.The steered molecular dynamics(SMD)simulation studies also suggested that the electrostatic potential,major groove width,and hydrogen bonds made major contribution to the DNA-specific recognition.In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand.This study indicates that the three-dimensional(3D)structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses,which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb,as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.展开更多
Silk fibroin(SF)as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity,tunable biodegradability,and high biocompatibility.Nowadays,various techniques have b...Silk fibroin(SF)as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity,tunable biodegradability,and high biocompatibility.Nowadays,various techniques have been developed for the applications of SF in bioengineering.Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films,hydrogels,and scaffolds.SF is also valuable as a coating on other substrate materials for biomedicine;however,there are few reviews related to SF-coated biomaterials.Thus,in this review,we focused on the surface modification of biomaterials using SF coatings,demonstrated their various preparation methods on substrate materials,and introduced the latest procedures.The diverse applications of SF coatings for biomedicine are discussed,including bone,ligament,skin,mucosa,and nerve regeneration,and dental implant surface modification.SF coating is conducive to inducing cell adhesion and migration,promoting hydroxyapatite(HA)deposition and matrix mineralization,and inhibiting the Notch signaling pathway,making it a promising strategy for bone regeneration.In addition,SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury.SF coating has been proven to enhance the mechanical properties of the substrate material,and render integral stability to the dressing material during the regeneration of skin and mucosa.Moreover,SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties,mechanical flexibility,and angiogenesis promotion effect.In addition,SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials.Thus,this review can be of great benefit for further improvements in SF-coated biomaterials,and will undoubtedly contribute to clinical transformation in the future.展开更多
Artificial intelligence(AI)has been utilized in soft-tissue analysis and prediction in orthodontic treatment planning,although its reliability has not been systematically assessed.This scoping review was conducted to ...Artificial intelligence(AI)has been utilized in soft-tissue analysis and prediction in orthodontic treatment planning,although its reliability has not been systematically assessed.This scoping review was conducted to outline the development of AI in terms of predicting soft-tissue changes after orthodontic treatment,as well as to comprehensively evaluate its prediction accuracy.Six electronic databases(PubMed,EBSCOhost,Web of Science,Embase,Cochrane Library,and Scopus)were searched up to March 14,2023.Clinical studies investigating the performance of AI-based systems in predicting post-orthodontic soft-tissue alterations were included.The Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2)and Joanna Briggs Institute(JBI)appraisal checklist for diagnostic test accuracy studies were applied to assess risk of bias,while the Grading of Recommendation,Assessment,Development,and Evaluation(GRADE)assessment was conducted to evaluate the certainty of outcomes.After screening 2500 studies,four non-randomized clinical trials were finally included for full-text evaluation.We found a low level of evidence indicating an estimated high overall accuracy of AI-generated prediction,whereas the lower lip and chin seemed to be the least predictable regions.Furthermore,the facial morphology simulated by AI via the fusion of multimodality images was considered to be reasonably true.Since all of the included studies that were not randomized clinical trials(non-RCTs)showed a moderate to high risk of bias,more well-designed clinical trials with sufficient sample size are needed in future work.展开更多
The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the“brain-oral axis”.A deeper understa...The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the“brain-oral axis”.A deeper understanding of the intricate interaction between the nervous system and the stomatognathic system is warranted,considering their significant developmental homology and anatomical proximity,and the more complex innervation of the jawbone compared to other skeletons.In this review,we provide an in-depth look at studies concerning neurodevelopment,craniofacial development,and congenital anomalies that occur when the two systems develop abnormally.It summarizes the cross-regulation between nerves and jawbones and the effects of various states of the jawbone on intrabony nerve distribution.Diseases closely related to both the nervous system and the stomatognathic system are divided into craniofacial diseases caused by neurological illnesses,and neurological diseases caused by an aberrant stomatognathic system.The two-way relationships between common diseases,such as periodontitis and neurodegenerative disorders,and depression and oral diseases were also discussed.This review provides valuable insights into novel strategies for neuro-skeletal tissue engineering and early prevention and treatment of orofacial and neurological diseases.展开更多
Currently, the primary treatment for hepatocellular carcinoma (HCC) is a comprehensive treatment based on surgery.1 In the case of advanced HCC that may not be removed surgically, additional issues, such as drug resis...Currently, the primary treatment for hepatocellular carcinoma (HCC) is a comprehensive treatment based on surgery.1 In the case of advanced HCC that may not be removed surgically, additional issues, such as drug resistance and drug inefficacy with long-term use of chemotherapeutic drugs, highlight the pressing need for new treatment strategies.2 Autophagy plays an essential role in cellular physiology, which was reported to modulate components of the immune system.3 Autophagy-related immune genes (ARIGs) are linked to both autophagy and immunity. Here we identified histone deacetylase 1 (HDAC1), an ARIG strongly expressed in HCC, as a therapeutic target.4 Then valproic acid (VPA), a specific inhibitor of HDAC1,5 was used to treat liver cancer in vitro and in vivo. The results demonstrated that VPA could significantly induce autophagy and apoptosis of Hepa1-6 cells and inhibit tumor growth in vivo. This effect could be related to the regulation of autophagy and tumor immune microenvironment by VPA.展开更多
基金This work was sponsored by the National Natural Science Foundation of China(No.52235007,52325504)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.T2121004).
文摘Implantable hydrogel-based bioelectronics(IHB)can precisely monitor human health and diagnose diseases.However,achieving biodegradability,biocompatibility,and high conformality with soft tissues poses significant challenges for IHB.Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues.This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film(GCF)with mechanical programmability.The regulation of GCF nearly covers soft tissue mechanics,an elastic modulus from 20 to 420 kPa,and a Poisson’s ratio from-0.25 to 0.52.The negative Poisson’s ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces.The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability.Notably,the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration.The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.
文摘Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.
基金supported by the Zhejiang Province Key Research and Development Program(No.2021C03059)。
文摘Large bone defect regeneration has always been recognized as a challenging clinical problem due to the difficulty of revascularization.Conventional treatments exhibit certain inherent disadvantages(e.g.,secondary injury,immunization,and potential infections).However,three-dimensional(3D)printing technology as an emerging field can serve as an effective approach to achieve satisfactory revascularization while making up for the above limitations.A wide variety of methods can be used to facilitate blood supply during the design of a 3D-printed scaffold.Importantly,the scaffold structure lays a foundation for the entire printing object;any method to promote angiogenesis can be effective only if it is based on well-designed scaffolds.In this review,different designs related to angiogenesis are summarized by collecting the literature from recent years.The 3D-printed scaffolds are classified into four major categories and discussed in detail,from elementary porous scaffolds to the most advanced bone-like scaffolds.Finally,structural design suggestions to achieve rapid angiogenesis are proposed by analyzing the above architectures.This review can provide a reference for organizations or individual academics to achieve improved bone defect repair and regeneration using 3D printing.
基金supported by the National Natural Science Foundation of China(Nos.8212200044,82071085,31872752,and 81600909)the Zhejiang Provincial Natu-ral Science Foundation of China(Nos.LR21H140001,LY22H140002,and LQ22C100003)+1 种基金the National Key Research and Development Pro-gram of China(No.2018YFA0703000)the Medical Technology and Education of Zhejiang Province of China(No.2018KY501).
文摘Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel strategy combining benidipine,an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects.Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety.The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus.After internalization into cells,the nanosystem is degraded by lysosomes,and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine,silicon and magnesium ions.Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts,indicating that it might be a potential approach in guiding bone repair in clinical applications.
基金supported by the National Natural Science Foundation Project(No.81771078 and No.81570982)Jiangsu Provincial Medical Innovation Team(No.CXTDB2017014)the Nanjing Clinical Research Center for Oral Diseases(No.2019060009)。
文摘Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years.Humanβ-defensin 3,a broad-spectrum antimicrobial peptide has been proven to have a variety of biological functions in periodontitis;however,relatively few reports have addressed the effects of human periodontal ligament cells(h PDLCs)on osteogenic differentiation.In this study,we evaluated the osteogenic effects of h PDLCs with an adenoviral vector encoding humanβ-defensin 3 in an inflammatory microenvironment.Then humanβ-defensin 3 gene-modified rat periodontal ligament cells were transplanted into rats with experimental periodontitis to observe their effects on periodontal bone repair.We found that the humanβ-defensin 3 gene-modified h PDLCs presented with high levels of osteogenesis-related gene expression and calcium deposition.Furthermore,the p38 MAPK pathway was activated in this process.In vivo,humanβ-defensin 3 gene-transfected rat PDLCs promoted bone repair in SD rats with periodontitis,and the p38 mitogen-activated protein kinase(MAPK)pathway might also have been involved.These findings demonstrate that humanβ-defensin 3 accelerates osteogenesis and that humanβ-defensin 3 gene modification may offer a potential approach to promote bone repair in patients with periodontitis.
基金National Natural Science Foundation of China,No.81801028Natural Science Foundation of Zhejiang Province,No.LQ19H140001.
文摘BACKGROUND Several previous studies have reported an unusual root formation in which a fractured apical fragment of an immature root continued to develop independent of the main root after trauma to an immature tooth.To date,there have been only rare reports of the continuing apical formation of the fractured root associated with dens evaginatus(DE).This paper presents a case of a separated root tip formation associated with a fractured tubercle of DE.CASE SUMMARY An 11-year-old boy was referred for gingival sinus on the buccal side of the right mandibular second premolar(tooth#45).Clinically,tooth#45 was free of caries,but there was a sign of a fractured tubercle of DE on the occlusal surface.Radiography showed that the root canal of tooth#45 was widely radiolucent.A separated root apex was found apically under the main root and was nearly completely formed with an apical orifice at the apical tip.Tooth#45 was diagnosed as tubular fracture of DE with chronic apical periodontitis.A revascularization technique was recommended to treat the tooth.At 3-mo and 1-yr follow-up,the patient remained asymptomatic.Periapical radiography revealed that the separated root tip distally drifted with closure of the apex.However,the root length and thickness of the main root did not increased.CONCLUSION Clinicians should be aware that even if tubercle of DE is fractured in an immature tooth,the root tip may be separated from the main root and completely formed.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LQ19H100004.
文摘BACKGROUND Transduodenal local excision is an alternative treatment approach for benign ampullary tumors.However,this procedure has technical difficulties,especially during reconstruction of the pancreaticobiliary ducts.An operating microscope has been widely used by surgeons for delicate surgery due to its major advantages of magnification,illumination,and stereoscopic view.The application of an operating microscope in transduodenal excision of ampullary tumors has not been reported.CASE SUMMARY A 55-year-old woman was admitted for investigation of recurrent upper abdominal pain.Physical examination and laboratory tests found no abnormalities.Imaging identified a large mass in the descending part of the duodenum.Esophagogastroduodenoscopy revealed a 3.5-cm-sized villous growth over the major duodenal papilla.Pathology of the endoscopic biopsy indicated a villous adenoma with low-grade dysplasia.Microscopic transduodenal excision of the ampullary tumor was performed.The final pathological diagnosis was villous-tubular adenoma with low-grade dysplasia.The patient was discharged on postoperative day 12 after an uneventful recovery.Endoscopic retrograde cholangiopancreatography was performed 3 mo postoperatively and showed no bile duct or pancreatic duct strictures and no tumor recurrence.The patient is continuing follow-up at our clinic and remains well.CONCLUSION Operating microscope-assisted transduodenal local excision is a feasible and effective option for benign ampullary tumors.
基金This work was financially supported by the National Key Research and Development Program of China(2018YFA0703000)the NationalNatural Science Foundation of China(81670972,31872752)+1 种基金Key Research and Development Program of Zhejiang,China(2017C01054,2018C03062,2017C01063)Postdoctoral Science Foundation of China(2020TQ0257,2020M681896).
文摘The organized alignment of cells in various tissues plays a significant role in the maintenance of specific functions.To induce such an alignment,ideal scaffolds should simulate the characteristics and morphologies of natural tissues.Aligned structures that guide cell orientation are used to facilitate tissue regeneration and repair.We here review how various aligned structures are fabricated,including aligned electrospun nanofibers,aligned porous or channeled structures,micropatterns and combinations thereof,and their application in nerve,skeletal muscle,tendon,and tubular dentin regeneration.The future use of aligned structures in tissue engineering is also discussed.
基金supported by the National Key R&D Program of China(No.2018YFC1105103)the Natural Science Foundation of Zhejiang Province,China(No.LY19H140004)the National Natural Science Foundation of China(Grant No.81771118)。
文摘Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal,but the details of these mechanisms remain unknown.Here,we investigated the expression patterns of a transcription factor,Krüppel-like factor 6(KLF6),during the development of murine tooth germ and its function in odontoblastic differentiation.KLF6 was almost ubiquitously expressed in odontoblasts at various stages,and it was co-expressed with P21(to varying degrees)in mouse dental germ.To determine the function of Klf6,overexpression and knockdown experiments were performed in a mouse dental papilla cell line(iMDP-3).Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of i MDP-3 through p21 upregulation.Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription.Additionally,the in vivo study showed that KLF6 and P21were also co-expressed in odontoblasts around the reparative dentin.In conclusion,Klf6 regulates the transcriptional activity of p21,thus promoting the cell proliferation to odontoblastic differentiation transition in vitro.This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.
基金supported by the Key Research and Development Program of Science and Technology Department of Zhejiang Province(No.2019C03081)。
文摘Considering the substantial role played by dendritic cells(DCs) in the immune system to bridge innate and adaptive immunity,studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces,their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns(BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins(HSPs) and high mobility group box 1(HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.
基金supported by the National Natural Science Foundations of China (Nos. 81972532, 81991500, 82101017, 81902778, and 81500864)Guangdong Basic and Applied Basic Research Foundation (2020A1515110741)
文摘The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy efficacy.However,few studies have explored exhausted T cell subpopulations in human cancers.In the present study,we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer(HNSCC)by multiplex immunohistochemistry(mIHC)to investigate two subsets of Tex,CD8+PD1+TCF1+progenitor exhausted T cells(TCF1+Texprog)and CD8+PD1+TCF1−terminally exhausted T cells(TCF1−Texterm).Moreover,fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells(Tregs)in the tumor immune microenvironment(TIME).mIHC and flow cytometry analysis showed that TCF1−Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients.TCF1+Texprog produced abundant TNFα,while TCF1−Texterm expressed higher levels of CD103,TIM-3,CTLA-4,and TIGIT.TCF1−Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+phenotype;and were associated with better overall survival and recurrence-free survival.The results also indicated that larger proportions of TCF1−Texterm were accompanied by an increase in the proportion of Tregs.Therefore,it was concluded that TCF1−Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival.A high proportion of TCF1−Texterm was associated with greater Treg abundance.
基金supported by the National Natural Science Foundation of China(Nos.81991500 and 81991502).
文摘Research in stomatology(dental medicine)continues to expand globally and is oriented towards solving clinical issues,focusing on clarifying the clinical relevance and potential mechanisms of oral–systemic connections via clinical epidemiology,oral microecological characterization,and the establishment of animal models.Interdisciplinary integration of materials science and tissue engineering with stomatology is expected to lead to the creation of innovative materials and technologies to better resolve the most prevalent and challenging clinical issues such as peri-implantitis,soft and hard tissue defects,and dentin hypersensitivity.With the rapid development of artificial intelligence(AI),5th generation mobile communication technology(5G),and big data applications,“intelligent stomatology”is emerging to build models for better clinical diagnosis and management,accelerate the reform of education,and support the growth and advancement of scientific research.Here,we summarized the current research status,and listed the future prospects and limitations of these three aspects,aiming to provide a basis for more accurate etiological exploration,novel treatment methods,and abundant big data analysis in stomatology to promote the translation of research achievements into practical applications for both clinicians and the public.
基金This work is supported by the National Key R&D Program of China(No.2022YFC2402900)the National Natural Science Foundation of China(No.81991502)+3 种基金the Key Research and Development Program of Zhejiang Province,China(No.2021C03074)the Basic Public Welfare Project of Zhejiang Province,China(No.LY22H140002)the Research and Development Program of the Stomatology Hospital,Zhejiang University School of Medicine(No.RD2022JCEL20)the Student Research Training Program of Zhejiang University School of Stomatology(No.2022S001).
文摘Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel.Collectively,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.
基金supported by grants from the National Natural Science Foundation of China(Nos 82001047,81672674,81872218,81321002,81402245)Research Funding from West China School/Hospital of Stomatology Sichuan University(No.RCDWJS2020-8)the 111 Project of MOE China(Grant No.B14038).
文摘Oral squamous cell carcinoma(OSCC)is one of the most common cancers worldwide,and with 354864 new cases each year.Cancer metastasis,recurrence,and drug resistance are the main causes to cripples and deaths of OSCC patients.As potent growth factors,fibroblast growth factors(FGFs)are frequently susceptible to being hijacked by cancer cells.In this study,we show that FGF8 is upregulated in OSCC tissues and high FGF8 expression is related with a set of clinicopathologic parameters,including age,drinking,and survival time.FGF8 treatment enhances the invasive capability of OSCC cells.Lentivirus-based FGF8 expression promotes OSCC metastasis in a mouse lung metastasis model.Further,mechanistic study demonstrates that FGF8 induces epithelial–mesenchymal transition(EMT)in OSCC cells.These results highlight a pro-metastatic function of FGF8,and underscore the role of FGF8 in OSCC development.
基金The study was supported by grants from the National Natural Science Foundation of China(No.82271026)the Key Research and Development Program of Science and Technology Department of Zhejiang Province(No.2019C03081).
文摘Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems.The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive.Here,a single-cell study involving 40043 cells is conducted,and a total of 10 distinct cell clusters are identified from five different groups.A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties.The increased immature neutrophils,Ly6C+CCR2hi monocytes,and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant.The enrichment of mature neutrophils,FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response.Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration.Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis.These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of‘osteoimmune-smart’biomaterials in the bone regeneration field.
基金supported by the National Key Research and Development Program of China(Nos.2022YFC2402900 and 2022YFC2402901)the Fundamental Research Funds for the Central Universities(No.226-2022-00213)the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMD23H300001).
文摘This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation.Therefore,we chose the chicken myeloid gene,mitochondrial import protein 1(mim-1),as a target to study the binding specificity between potential dual-Myb-binding sites.The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT,which contains two AACNG consensuses.Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand(complex F)is more stable than that in the reverse strand(complex R).The principal component analysis(PCA)dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3(R2R3),resulting in the dissociation of DNA from c-Myb in complex R at 330 K,triggered by the reduced electrostatic potential on the surface of R2R3.Furthermore,the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R,which affected on the hydrogenbond formation ability between R2R3 and DNA,and directly resulted in the dissociation of DNA from R2R3.The steered molecular dynamics(SMD)simulation studies also suggested that the electrostatic potential,major groove width,and hydrogen bonds made major contribution to the DNA-specific recognition.In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand.This study indicates that the three-dimensional(3D)structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses,which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb,as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.
基金supported by the National Natural Science Foundation of China (No.82101062)the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (No.2023KY132)the Zhejiang Provincial Key Research and Development Program of China (No.2021C03113).
文摘Silk fibroin(SF)as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity,tunable biodegradability,and high biocompatibility.Nowadays,various techniques have been developed for the applications of SF in bioengineering.Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films,hydrogels,and scaffolds.SF is also valuable as a coating on other substrate materials for biomedicine;however,there are few reviews related to SF-coated biomaterials.Thus,in this review,we focused on the surface modification of biomaterials using SF coatings,demonstrated their various preparation methods on substrate materials,and introduced the latest procedures.The diverse applications of SF coatings for biomedicine are discussed,including bone,ligament,skin,mucosa,and nerve regeneration,and dental implant surface modification.SF coating is conducive to inducing cell adhesion and migration,promoting hydroxyapatite(HA)deposition and matrix mineralization,and inhibiting the Notch signaling pathway,making it a promising strategy for bone regeneration.In addition,SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury.SF coating has been proven to enhance the mechanical properties of the substrate material,and render integral stability to the dressing material during the regeneration of skin and mucosa.Moreover,SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties,mechanical flexibility,and angiogenesis promotion effect.In addition,SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials.Thus,this review can be of great benefit for further improvements in SF-coated biomaterials,and will undoubtedly contribute to clinical transformation in the future.
基金supported by the Research Grants Council of the Hong Kong,China (No.17109619).
文摘Artificial intelligence(AI)has been utilized in soft-tissue analysis and prediction in orthodontic treatment planning,although its reliability has not been systematically assessed.This scoping review was conducted to outline the development of AI in terms of predicting soft-tissue changes after orthodontic treatment,as well as to comprehensively evaluate its prediction accuracy.Six electronic databases(PubMed,EBSCOhost,Web of Science,Embase,Cochrane Library,and Scopus)were searched up to March 14,2023.Clinical studies investigating the performance of AI-based systems in predicting post-orthodontic soft-tissue alterations were included.The Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2)and Joanna Briggs Institute(JBI)appraisal checklist for diagnostic test accuracy studies were applied to assess risk of bias,while the Grading of Recommendation,Assessment,Development,and Evaluation(GRADE)assessment was conducted to evaluate the certainty of outcomes.After screening 2500 studies,four non-randomized clinical trials were finally included for full-text evaluation.We found a low level of evidence indicating an estimated high overall accuracy of AI-generated prediction,whereas the lower lip and chin seemed to be the least predictable regions.Furthermore,the facial morphology simulated by AI via the fusion of multimodality images was considered to be reasonably true.Since all of the included studies that were not randomized clinical trials(non-RCTs)showed a moderate to high risk of bias,more well-designed clinical trials with sufficient sample size are needed in future work.
基金supported by the Key Research and Development Program in Zhejiang Province(No.2021C03059)the Funds of the Central Government Guiding Local Science and Technology Development(No.2023ZY1060)National Natural Science Foundation of China(No.81801011).
文摘The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the“brain-oral axis”.A deeper understanding of the intricate interaction between the nervous system and the stomatognathic system is warranted,considering their significant developmental homology and anatomical proximity,and the more complex innervation of the jawbone compared to other skeletons.In this review,we provide an in-depth look at studies concerning neurodevelopment,craniofacial development,and congenital anomalies that occur when the two systems develop abnormally.It summarizes the cross-regulation between nerves and jawbones and the effects of various states of the jawbone on intrabony nerve distribution.Diseases closely related to both the nervous system and the stomatognathic system are divided into craniofacial diseases caused by neurological illnesses,and neurological diseases caused by an aberrant stomatognathic system.The two-way relationships between common diseases,such as periodontitis and neurodegenerative disorders,and depression and oral diseases were also discussed.This review provides valuable insights into novel strategies for neuro-skeletal tissue engineering and early prevention and treatment of orofacial and neurological diseases.
文摘Currently, the primary treatment for hepatocellular carcinoma (HCC) is a comprehensive treatment based on surgery.1 In the case of advanced HCC that may not be removed surgically, additional issues, such as drug resistance and drug inefficacy with long-term use of chemotherapeutic drugs, highlight the pressing need for new treatment strategies.2 Autophagy plays an essential role in cellular physiology, which was reported to modulate components of the immune system.3 Autophagy-related immune genes (ARIGs) are linked to both autophagy and immunity. Here we identified histone deacetylase 1 (HDAC1), an ARIG strongly expressed in HCC, as a therapeutic target.4 Then valproic acid (VPA), a specific inhibitor of HDAC1,5 was used to treat liver cancer in vitro and in vivo. The results demonstrated that VPA could significantly induce autophagy and apoptosis of Hepa1-6 cells and inhibit tumor growth in vivo. This effect could be related to the regulation of autophagy and tumor immune microenvironment by VPA.
