Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration.At present,autograft harvest procedures may cause secondary trauma to patients,while bone scaffo...Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration.At present,autograft harvest procedures may cause secondary trauma to patients,while bone scaffold materials lack osteogenic activity,resulting in a limited application.Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft,but the explosive release of growth factor may also cause side effects.In this study,we innovatively used platelet-rich fibrin(PRF)-modified bone scaffolds(Bio-Oss®)to replace autograft,and used cytokine(BMP-2)to enhance osteogenesis.Encouragingly,this mixture,which we named“Autograft Mimic(AGM)”,has multiple functions and advantages.(1)The fiber network provided by PRF binds the entire bone scaffold together,thereby shaping the bone grafts and maintaining the space of the defect area.(2)The sustained release of BMP-2 from bone graft promoted bone regeneration continuously.(3)AGM recruited bone marrow mesenchymal stem cells(BMSCs)and promote their proliferation,migration,and osteogenic differentiation.Thus,AGM developed in this study can improve osteogenesis,and provide new guidance for the development of clinical bone grafts.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
We report a new facile light-induced strategy to disperse micron-sized aggregated bulk covalent organic frameworks(COFs)into isolated COFs nanoparticles.This was achieved by a series of metal-coordinated COFs,namely C...We report a new facile light-induced strategy to disperse micron-sized aggregated bulk covalent organic frameworks(COFs)into isolated COFs nanoparticles.This was achieved by a series of metal-coordinated COFs,namely COF-909-Cu,-Co or-Fe,where for the first time the diffusio-phoretic propulsion was utilized to design COF-based micro/nanomotors.The mechanism studies revealed that the metal ions decorated in the COF-909 backbone could promote the separation of electron and holes and trigger the production of sufficient ionic and reactive oxygen species under visible light irradiation.In this way,strong light-induced self-diffusiophoretic effect is achieved,resulting in good dispersion of COFs.Among them,COF-909-Fe showed the highest dispersion performance,along with a drastic decrease in particle size from 5μm to500 nm,within only 30 min light irradiation,which is inaccessible by using traditional magnetic stirring or ultrasonication methods.More importantly,benefiting from the outstanding dispersion efficiency,COF-909-Fe micro/nanomotors were demonstrated to be efficient in photocatalytic degradation of tetracycline,about 8 times faster than using traditional magnetic stirring method.This work opens up a new avenue to prepare isolated nanosized COFs in a high-fast,simple,and green manner.展开更多
Periodontal bone regeneration is a major challenge in the treatment of periodontitis.Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed b...Periodontal bone regeneration is a major challenge in the treatment of periodontitis.Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation,via conventional treatment.CD301b^(+)macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment,but their role in periodontal bone repair has not been reported.展开更多
Digital guided therapy(DGT)has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades.The concept of DGT for endodontic diseases is categorized into static guided ...Digital guided therapy(DGT)has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades.The concept of DGT for endodontic diseases is categorized into static guided endodontics(SGE),necessitating a meticulously designed template,and dynamic guided endodontics(DGE),which utilizes an optical triangulation tracking system.Based on cone-beam computed tomography(CBCT)images superimposed with or without oral scan(OS)data,a virtual template is crafted through software and subsequently translated into a 3-dimensional(3D)printing for SGE,while the system guides the drilling path with a real-time navigation in DGE.DGT was reported to resolve a series of challenging endodontic cases,including teeth with pulp obliteration,teeth with anatomical abnormalities,teeth requiring retreatment,posterior teeth needing endodontic microsurgery,and tooth autotransplantation.Case reports and basic researches all demonstrate that DGT stand as a precise,time-saving,and minimally invasive approach in contrast to conventional freehand method.This expert consensus mainly introduces the case selection,general workflow,evaluation,and impact factor of DGT,which could provide an alternative working strategy in endodontic treatment.展开更多
Dental Caries is a kind of chronic oral disease that greatly threaten human being’s health.Though dentists and researchers struggled for decades to combat this oral disease,the incidence and prevalence of dental cari...Dental Caries is a kind of chronic oral disease that greatly threaten human being’s health.Though dentists and researchers struggled for decades to combat this oral disease,the incidence and prevalence of dental caries remain quite high.Therefore,improving the disease management is a key issue for the whole population and life cycle management of dental caries.So clinical difficulty assessment system of caries prevention and management is established based on dental caries diagnosis and classification.Dentists should perform oral examination and establish dental records at each visit.When treatment plan is made on the base of caries risk assessment and carious lesion activity,we need to work out patient-centered and personalized treatment planning to regain oral microecological balance,to control caries progression and to restore the structure and function of the carious teeth.And the follow-up visits are made based on personalized caries management.This expert consensus mainly discusses caries risk assessment,caries treatment difficulty assessment and dental caries treatment plan,which are the most important parts of caries management in the whole life cycle.展开更多
Regenerative endodontic procedures(REPs)is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis.The ultimate objective of REPs is to regenerate the pulp-dentin complex,extend t...Regenerative endodontic procedures(REPs)is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis.The ultimate objective of REPs is to regenerate the pulp-dentin complex,extend the tooth longevity and restore the normal function.Scientific evidence has demonstrated the efficacy of REPs in promotion of root development through case reports,case series,cohort studies,and randomized controlled studies.However,variations in clinical protocols for REPs exist due to the empirical nature of the original protocols and rapid advancements in the research field of regenerative endodontics.The heterogeneity in protocols may cause confusion among dental practitioners,thus guidelines and considerations of REPs should be explicated.This expert consensus mainly discusses the biological foundation,the available clinical protocols and current status of REPs in treating immature teeth with pulp necrosis,as well as the main complications of this treatment,aiming at refining the clinical management of REPs in accordance with the progress of basic researches and clinical studies,suggesting REPs may become a more consistently evidence-based option in dental treatment.展开更多
Dental stem cells(DSCs), an important source of mesenchymal stem cells(MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attribut...Dental stem cells(DSCs), an important source of mesenchymal stem cells(MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles(DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the(Ⅰ) distinguishing features of DSC-EVs compared with other types of MSC-EVs,(Ⅱ)heterogeneity among different subtypes of DSC-derived EVs,(Ⅲ) action modes of DSC-EVs,(Ⅳ) standardization for eligible DSC-EVs and(Ⅴ) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.展开更多
In an attempt to overcome the limitations of titanium in dental and orthopaedic clinical applications, a new method has been developed to prepare calcium carbonate coatings on sandblasted and acid-etched(SA) titanium ...In an attempt to overcome the limitations of titanium in dental and orthopaedic clinical applications, a new method has been developed to prepare calcium carbonate coatings on sandblasted and acid-etched(SA) titanium implants. The purpose of this study was to investigate the effect of calcium carbonate-SA(CC-SA) implants on osseointegration in vivo. The surfaces of SA and CC-SA implants were characterised for surface morphology and surface chemistry. Subsequently, these two kinds of implants were implanted in the femoral condyles of rabbits. The implants were retrieved and prepared for histological and histomorphometric evaluation 1, 2, 4, 8 and 12 weeks after implantation. Significantly higher values of bone-to-implant contact of the entire implant except the gap area(BIC_ALL) and the bone-to-implant contact of the gap area(BIC_GAP) were found in animals with the CC-SA implants than in those with the SA implants at 4 weeks. Higher values of total gap bone were found in those with the CC-SA implants than in those with the SA implants at 1, 2 and 4 weeks. In conclusion, the current findings demonstrate that the calcium carbonate coating can improve and accelerate the early ingrowth of bone and osseointegration at the early healing phase. This may reduce clinical healing times and thus improve implant success rates.展开更多
Immune checkpoint blockade(ICB)therapy has recently shown promise in treating several malignancies.However,only a limited number of patients respond to this treatment,partially because of the“immune cold”condition o...Immune checkpoint blockade(ICB)therapy has recently shown promise in treating several malignancies.However,only a limited number of patients respond to this treatment,partially because of the“immune cold”condition of the tumor immune microenvironment.Pyroptosis is a type of gasdermin-mediated programmed cell death that often leads to inflammation and immune responses.Many studies on the mechanism and function of pyroptosis have led to increasing recognition of the role of pyroptosis in malignant progression and immune therapy.Pyroptosis has the potential to alter the tumor immune microenvironment by releasing tumor-associated antigens,damage-associated molecular patterns,and proinflammatory cytokines,thus leading to intratumoral inflammatory responses,stimulation of tumor-specific cytotoxic T cell infiltration,conversion of“cold”to“hot”tumors,and ultimately improving the efficacy of ICB therapy.Some cancer treatments have been shown to restore anticancer immunosurveillance through the induction of pyroptosis.Therapy promoting pyroptosis and ICB therapy may have synergistic effects in cancer treatment.This review summarizes the mechanisms and roles of pyroptosis in the tumor microenvironment and combination treatment strategies.An improved understanding of the roles of pyroptosis in tumorigenesis,immune evasion,and treatment would aid in the development of therapeutic strategies for malignancies.展开更多
The emergence and clinical application of immunotherapy is considered a promising breakthrough in cancer treatment.According to the literature,immune checkpoint blockade(ICB)has achieved positive clinical responses in...The emergence and clinical application of immunotherapy is considered a promising breakthrough in cancer treatment.According to the literature,immune checkpoint blockade(ICB)has achieved positive clinical responses in different cancer types,although its clinical efficacy remains limited in some patients.The main obstacle to inducing effective antitumor immune responses with ICB is the development of an immunosuppressive tumor microenvironment.Myeloid-derived suppressor cells(MDSCs),as major immune cells that mediate tumor immunosuppression,are intimately involved in regulating the resistance of cancer patients to ICB therapy and to clinical cancer staging and prognosis.Therefore,a combined treatment strategy using MDSC inhibitors and ICB has been proposed and continually improved.This article discusses the immunosuppressive mechanism,clinical significance,and visualization methods of MDSCs.More importantly,it describes current research progress on compounds targeting MDSCs to enhance the antitumor efficacy of ICB.展开更多
Pyroptosis is a form of proinflammatory cell death that depends on the gasdermin family of proteins.The main features of pyroptosis are altered membrane permeability,cell swelling,membrane rupture,and the ability to m...Pyroptosis is a form of proinflammatory cell death that depends on the gasdermin family of proteins.The main features of pyroptosis are altered membrane permeability,cell swelling,membrane rupture,and the ability to mobilize a strong immune response.The relationship between pyroptosis and cancer has become a popular topic in immunological research.Multiple strategies for inducing pyroptosis in cancer cells have been developed for cancer therapy,including chemotherapy,small molecule drugs,and nanomedicines.In this review,we systematically discuss recent advances in research on the mechanisms of pyroptosis,and compare pyroptosis with apoptosis and necroptosis from several aspects.The development of various experimental systems has accompanied rapid progress in this field,but little consensus on monitoring pyroptosis is currently available.We focus on techniques commonly used to monitor pyroptosis,and describe future techniques that may be used to increase our knowledge in this field.Overall,the advancement of pyroptosis detection methods will help researchers to better investigate the relationships between pyroptosis and various cancers,and should provide insights into the use of these promising tools for cancer treatments.展开更多
Periodontitis,as a chronic inflammatory disease,remains unsolved,and the pathogenesis of this disease has not been fully elucidated.In this study,the effect of miR-4262 was investigated in tumor necrosis factor-α(TNF...Periodontitis,as a chronic inflammatory disease,remains unsolved,and the pathogenesis of this disease has not been fully elucidated.In this study,the effect of miR-4262 was investigated in tumor necrosis factor-α(TNF-α)induced human periodontal stem cells(hPDLSCs)for the first time.The gene expression involved in this study was determined using polymerase chain reaction(PCR),the expressions of relevant proteins were determined by western blot analysis,and the levels of IL-1β,IL-6,and MCP-1 were estimated by enzyme-linked immunosorbent assay(ELISA)assay.The luciferase reporter assay was performed for verification of the target gene,alkaline phosphatase(ALP)activity detection was used for differentiation capacity,and alizarin red staining assay was used for mineralization capacity.The inhibition of miRNA-4262,which resulted in the upregulation of suppressor of cytokine signaling 4(SOCS4),showed protective effects,including anti-inflammation and promotional effects on osteogenesis as well as differentiation in TNF-αinduced hPDLSCs.These results provided insights into the roles of miRNAs in regulating the inflammatory response,differentiation,and osteogenesis in hPDLSCs,which may promote the understanding of the mechanisms of periodontitis and find out a better therapeutic application.展开更多
Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,su...Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term circulation.With the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against cancer.In this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer therapy.The original sources,methods for obtaining PDNVs,composition and structure are introduced systematically.With an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail.Finally,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.展开更多
The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumo...The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.展开更多
The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(...The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.展开更多
Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy...Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy can ultimately relapse and progress.Thus,some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy.Recently,multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response;thus,vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes.A successful antitumor immune response requires an intact“Cancer-Immunity Cycle,”including T cell priming and activation,immune cell recruitment,and recognition and killing of cancer cells.Angiogenic inducers,especially vascular endothelial growth factor(VEGF),can interfere with activation,infiltration,and function of T cells,thus breaking the“Cancer-Immunity Cycle.”Together with immunostimulation-regulated tumor vessel remodeling,VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors.Following the successes of recent landmark phase III clinical trials,therapies combining immune checkpoint inhibitors(ICIs)with antiangiogenic agents have become first-line treatments for multiple solid tumors,whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies.In this review,we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies.Then,we discussed recent progress in randomized clinical trials.ICI-containing combinations were the focus of this review because of their recent successes,but combinations containing other immunotherapies were also discussed.Finally,we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate collaboration within the research community.展开更多
Postmenopausal osteoporosis is a common chronic dynamic bone disorder,caused by estrogen deficiency.To address this issue,we constructed a controlled drug-release system composed of poly(N-isopropylacrylamide)brush mo...Postmenopausal osteoporosis is a common chronic dynamic bone disorder,caused by estrogen deficiency.To address this issue,we constructed a controlled drug-release system composed of poly(N-isopropylacrylamide)brush modified mesoporous hydroxyapatite(MHA-SIM-P)loaded with simvastatin(SIM)using an ovariectomised(OVX)rat model.Quantitative alkaline phosphatase activity assay,alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro.The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells(BMSCs)in vitro.In osteoporotic animal model,the therapeutic efficiency for bone defect was evaluated byμCT analysis,tartrateresistant acid phosphatase,haematoxylin and eosin staining,which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks.This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis.Thus,this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.展开更多
In a recent study published in Science,Tsvetkov et al1.shed a light on a new form of cell death,copper-dependent cell death(termed cuproptosis).They defined“cuproptosis”as a nonapoptotic cell death pathway.They have...In a recent study published in Science,Tsvetkov et al1.shed a light on a new form of cell death,copper-dependent cell death(termed cuproptosis).They defined“cuproptosis”as a nonapoptotic cell death pathway.They have demonstrated that copper directly binds to lipoylated components of the tricarboxylic acid(TCA)cycle.Then aggregation of these copper-bound,lipoylated mitochondrial proteins and subsequent Fe-S cluster protein loss triggered proteotoxic stress and a distinct form of cell death.展开更多
Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a deat...Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a death mode of tumor cells that can promote tumor immunity.ICD can induce strong an-titumor immune responses through the ectopic exposure of calreticulin on the plasma membrane surface and the release of the non-histone nuclear protein high-mobility group box 1(HMGB1),ATP,and in-terferon(IFN),thus activating an adaptive immune response against dead cell-associated antigens and enhancing the therapeutic effect of tumor immunotherapy.Chemotherapy,radiotherapy,photothermal therapy,magneto-thermodynamics therapy,nanopulse stimulation,and oncolytic virus therapy can all induce a strong antitumor immune response by ICD.In addition,the application of nanotechnology can precisely target drug delivery and improve the efficacy of immunotherapy.Here we introduce the basic concepts and molecular mechanisms underlying the induction of ICD.Then,we summarize and discuss the progress in the application of nanotechnology in immunotherapy to promote ICD.Finally,we attempt to define the challenges and future directions in this area to extend the benefits of ICD to a broader patient population.展开更多
基金the National Natural Science Foundation of China(Grant No.82071095,31570982).
文摘Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration.At present,autograft harvest procedures may cause secondary trauma to patients,while bone scaffold materials lack osteogenic activity,resulting in a limited application.Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft,but the explosive release of growth factor may also cause side effects.In this study,we innovatively used platelet-rich fibrin(PRF)-modified bone scaffolds(Bio-Oss®)to replace autograft,and used cytokine(BMP-2)to enhance osteogenesis.Encouragingly,this mixture,which we named“Autograft Mimic(AGM)”,has multiple functions and advantages.(1)The fiber network provided by PRF binds the entire bone scaffold together,thereby shaping the bone grafts and maintaining the space of the defect area.(2)The sustained release of BMP-2 from bone graft promoted bone regeneration continuously.(3)AGM recruited bone marrow mesenchymal stem cells(BMSCs)and promote their proliferation,migration,and osteogenic differentiation.Thus,AGM developed in this study can improve osteogenesis,and provide new guidance for the development of clinical bone grafts.
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 Huazhong University of Science and Technology(No.2021XXJS036,3004013134)National Natural Science Foundation of China(No.51903099,82002879,22102059)+2 种基金the Innovation and Talent Recruitment Base of New Energy Chemistry and Device(No.B21003)China Postdoctoral Science Foundation(2021M692475,2021T140524,XJ2021037)support from the 100 Talents Program of the Hubei Provincial Government。
文摘We report a new facile light-induced strategy to disperse micron-sized aggregated bulk covalent organic frameworks(COFs)into isolated COFs nanoparticles.This was achieved by a series of metal-coordinated COFs,namely COF-909-Cu,-Co or-Fe,where for the first time the diffusio-phoretic propulsion was utilized to design COF-based micro/nanomotors.The mechanism studies revealed that the metal ions decorated in the COF-909 backbone could promote the separation of electron and holes and trigger the production of sufficient ionic and reactive oxygen species under visible light irradiation.In this way,strong light-induced self-diffusiophoretic effect is achieved,resulting in good dispersion of COFs.Among them,COF-909-Fe showed the highest dispersion performance,along with a drastic decrease in particle size from 5μm to500 nm,within only 30 min light irradiation,which is inaccessible by using traditional magnetic stirring or ultrasonication methods.More importantly,benefiting from the outstanding dispersion efficiency,COF-909-Fe micro/nanomotors were demonstrated to be efficient in photocatalytic degradation of tetracycline,about 8 times faster than using traditional magnetic stirring method.This work opens up a new avenue to prepare isolated nanosized COFs in a high-fast,simple,and green manner.
基金supported by the National Natural Science Foundation of China(82025011,82220108018,82100975,82270981)the Fundamental Research Funds for the Central Universities(2042021kf0181)。
文摘Periodontal bone regeneration is a major challenge in the treatment of periodontitis.Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation,via conventional treatment.CD301b^(+)macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment,but their role in periodontal bone repair has not been reported.
文摘Digital guided therapy(DGT)has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades.The concept of DGT for endodontic diseases is categorized into static guided endodontics(SGE),necessitating a meticulously designed template,and dynamic guided endodontics(DGE),which utilizes an optical triangulation tracking system.Based on cone-beam computed tomography(CBCT)images superimposed with or without oral scan(OS)data,a virtual template is crafted through software and subsequently translated into a 3-dimensional(3D)printing for SGE,while the system guides the drilling path with a real-time navigation in DGE.DGT was reported to resolve a series of challenging endodontic cases,including teeth with pulp obliteration,teeth with anatomical abnormalities,teeth requiring retreatment,posterior teeth needing endodontic microsurgery,and tooth autotransplantation.Case reports and basic researches all demonstrate that DGT stand as a precise,time-saving,and minimally invasive approach in contrast to conventional freehand method.This expert consensus mainly introduces the case selection,general workflow,evaluation,and impact factor of DGT,which could provide an alternative working strategy in endodontic treatment.
基金supported by National Natural Science Foundation of China[81870759]。
文摘Dental Caries is a kind of chronic oral disease that greatly threaten human being’s health.Though dentists and researchers struggled for decades to combat this oral disease,the incidence and prevalence of dental caries remain quite high.Therefore,improving the disease management is a key issue for the whole population and life cycle management of dental caries.So clinical difficulty assessment system of caries prevention and management is established based on dental caries diagnosis and classification.Dentists should perform oral examination and establish dental records at each visit.When treatment plan is made on the base of caries risk assessment and carious lesion activity,we need to work out patient-centered and personalized treatment planning to regain oral microecological balance,to control caries progression and to restore the structure and function of the carious teeth.And the follow-up visits are made based on personalized caries management.This expert consensus mainly discusses caries risk assessment,caries treatment difficulty assessment and dental caries treatment plan,which are the most important parts of caries management in the whole life cycle.
文摘Regenerative endodontic procedures(REPs)is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis.The ultimate objective of REPs is to regenerate the pulp-dentin complex,extend the tooth longevity and restore the normal function.Scientific evidence has demonstrated the efficacy of REPs in promotion of root development through case reports,case series,cohort studies,and randomized controlled studies.However,variations in clinical protocols for REPs exist due to the empirical nature of the original protocols and rapid advancements in the research field of regenerative endodontics.The heterogeneity in protocols may cause confusion among dental practitioners,thus guidelines and considerations of REPs should be explicated.This expert consensus mainly discusses the biological foundation,the available clinical protocols and current status of REPs in treating immature teeth with pulp necrosis,as well as the main complications of this treatment,aiming at refining the clinical management of REPs in accordance with the progress of basic researches and clinical studies,suggesting REPs may become a more consistently evidence-based option in dental treatment.
基金funded by the National Natural Science Foundation of China (81922038, 81870361, 81671816)China Postdoctoral Innovation Science Foundation (BX20200254)+3 种基金National Key R&D Program of China (2019YFA0210500)Applied Basic Research Project of Wuhan Municipal Science and Technology Bureau (2020020601012249)Hubei Natural Science Foundation Outstanding Young Talents Project (2020CFA068)China Postdoctoral Science Foundation (2021M692474)
文摘Dental stem cells(DSCs), an important source of mesenchymal stem cells(MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles(DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the(Ⅰ) distinguishing features of DSC-EVs compared with other types of MSC-EVs,(Ⅱ)heterogeneity among different subtypes of DSC-derived EVs,(Ⅲ) action modes of DSC-EVs,(Ⅳ) standardization for eligible DSC-EVs and(Ⅴ) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.
基金funded by the National Natural Science Foundation of China(nos 81200812 and 81371170)the Foundation of Health and the family planning commission of Hubei province(no.WJ2015MB276)
文摘In an attempt to overcome the limitations of titanium in dental and orthopaedic clinical applications, a new method has been developed to prepare calcium carbonate coatings on sandblasted and acid-etched(SA) titanium implants. The purpose of this study was to investigate the effect of calcium carbonate-SA(CC-SA) implants on osseointegration in vivo. The surfaces of SA and CC-SA implants were characterised for surface morphology and surface chemistry. Subsequently, these two kinds of implants were implanted in the femoral condyles of rabbits. The implants were retrieved and prepared for histological and histomorphometric evaluation 1, 2, 4, 8 and 12 weeks after implantation. Significantly higher values of bone-to-implant contact of the entire implant except the gap area(BIC_ALL) and the bone-to-implant contact of the gap area(BIC_GAP) were found in animals with the CC-SA implants than in those with the SA implants at 4 weeks. Higher values of total gap bone were found in those with the CC-SA implants than in those with the SA implants at 1, 2 and 4 weeks. In conclusion, the current findings demonstrate that the calcium carbonate coating can improve and accelerate the early ingrowth of bone and osseointegration at the early healing phase. This may reduce clinical healing times and thus improve implant success rates.
基金supported by the National Natural Science Foundation of China 82072996(Z.S.),81874131(Z.S.),82170941(L.Z.)National Key Research and Development Program(2017YFSF090107)the Innovative research team of high-level local universities in Shanghai ZLCX20180500(Z.S.).
文摘Immune checkpoint blockade(ICB)therapy has recently shown promise in treating several malignancies.However,only a limited number of patients respond to this treatment,partially because of the“immune cold”condition of the tumor immune microenvironment.Pyroptosis is a type of gasdermin-mediated programmed cell death that often leads to inflammation and immune responses.Many studies on the mechanism and function of pyroptosis have led to increasing recognition of the role of pyroptosis in malignant progression and immune therapy.Pyroptosis has the potential to alter the tumor immune microenvironment by releasing tumor-associated antigens,damage-associated molecular patterns,and proinflammatory cytokines,thus leading to intratumoral inflammatory responses,stimulation of tumor-specific cytotoxic T cell infiltration,conversion of“cold”to“hot”tumors,and ultimately improving the efficacy of ICB therapy.Some cancer treatments have been shown to restore anticancer immunosurveillance through the induction of pyroptosis.Therapy promoting pyroptosis and ICB therapy may have synergistic effects in cancer treatment.This review summarizes the mechanisms and roles of pyroptosis in the tumor microenvironment and combination treatment strategies.An improved understanding of the roles of pyroptosis in tumorigenesis,immune evasion,and treatment would aid in the development of therapeutic strategies for malignancies.
基金This work was supported by the National Nature Science Foundation of China(Grant Nos.82072996,81874131,and 81672668)Innovative Research Team of High-level Local Universities in Shanghai(Grant No.SSMU-ZLCX20180500)+1 种基金supported by Fundamental Research Funds for the Central Universities of China(Grant No.2042017kf0171)(Outstanding Young Researchers)Hubei Province Nature Science Funds for Distinguished Young Scholar(Grant No.2017CFA062)。
文摘The emergence and clinical application of immunotherapy is considered a promising breakthrough in cancer treatment.According to the literature,immune checkpoint blockade(ICB)has achieved positive clinical responses in different cancer types,although its clinical efficacy remains limited in some patients.The main obstacle to inducing effective antitumor immune responses with ICB is the development of an immunosuppressive tumor microenvironment.Myeloid-derived suppressor cells(MDSCs),as major immune cells that mediate tumor immunosuppression,are intimately involved in regulating the resistance of cancer patients to ICB therapy and to clinical cancer staging and prognosis.Therefore,a combined treatment strategy using MDSC inhibitors and ICB has been proposed and continually improved.This article discusses the immunosuppressive mechanism,clinical significance,and visualization methods of MDSCs.More importantly,it describes current research progress on compounds targeting MDSCs to enhance the antitumor efficacy of ICB.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.82072996,82170941,and 81874131)the National Key Research and Development Program(Grant No.2017YFSF090107)+1 种基金the Hubei Province Natural Science Funds for Distinguished Young Scholar(Grant No.2017CFA062)the Innovative Research Team of High-level Local Universities in Shanghai(Grant No.ZLCX20180500).
文摘Pyroptosis is a form of proinflammatory cell death that depends on the gasdermin family of proteins.The main features of pyroptosis are altered membrane permeability,cell swelling,membrane rupture,and the ability to mobilize a strong immune response.The relationship between pyroptosis and cancer has become a popular topic in immunological research.Multiple strategies for inducing pyroptosis in cancer cells have been developed for cancer therapy,including chemotherapy,small molecule drugs,and nanomedicines.In this review,we systematically discuss recent advances in research on the mechanisms of pyroptosis,and compare pyroptosis with apoptosis and necroptosis from several aspects.The development of various experimental systems has accompanied rapid progress in this field,but little consensus on monitoring pyroptosis is currently available.We focus on techniques commonly used to monitor pyroptosis,and describe future techniques that may be used to increase our knowledge in this field.Overall,the advancement of pyroptosis detection methods will help researchers to better investigate the relationships between pyroptosis and various cancers,and should provide insights into the use of these promising tools for cancer treatments.
文摘Periodontitis,as a chronic inflammatory disease,remains unsolved,and the pathogenesis of this disease has not been fully elucidated.In this study,the effect of miR-4262 was investigated in tumor necrosis factor-α(TNF-α)induced human periodontal stem cells(hPDLSCs)for the first time.The gene expression involved in this study was determined using polymerase chain reaction(PCR),the expressions of relevant proteins were determined by western blot analysis,and the levels of IL-1β,IL-6,and MCP-1 were estimated by enzyme-linked immunosorbent assay(ELISA)assay.The luciferase reporter assay was performed for verification of the target gene,alkaline phosphatase(ALP)activity detection was used for differentiation capacity,and alizarin red staining assay was used for mineralization capacity.The inhibition of miRNA-4262,which resulted in the upregulation of suppressor of cytokine signaling 4(SOCS4),showed protective effects,including anti-inflammation and promotional effects on osteogenesis as well as differentiation in TNF-αinduced hPDLSCs.These results provided insights into the roles of miRNAs in regulating the inflammatory response,differentiation,and osteogenesis in hPDLSCs,which may promote the understanding of the mechanisms of periodontitis and find out a better therapeutic application.
基金This work was supported by the National Natural Science Foundation of China(Nos.81972547 and 82273306)the Hubei Province health and family planning scientific research project(WJ2023Q011,China).
文摘Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term circulation.With the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against cancer.In this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer therapy.The original sources,methods for obtaining PDNVs,composition and structure are introduced systematically.With an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail.Finally,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.
基金financially supported by National Natural Science Foundation of China(51703187,81874131,and 81672668)the Chongqing Talent Plan for Young Top Notch Talents(CQYC202005029,China)+2 种基金Major State Basic Research Development Program of China(2017YFA0205201 and 2018YFA0107301)National Key Research and Development Program(2017YFSF090107,China)the Hubei Province Natural Science Funds for Distinguished Young Scholar 2017CFA062。
文摘The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.
基金This work was supported by the National Natural Science Foundation of China(Nos.82072996(Z.J.S.)81874131(Z.J.S.)+1 种基金81702730(L.L.B.),and 51973076(G.Y.))the Fundamental Research Funds for the Central Universities(No.2042021kf0216)to Z.J.S.,China Postdoctoral Science Foundation(Nos.2018M630883 and 2019T120688)to L.L.B.,and Wuhan Young Medical Talents Training Project to L.L.B.
文摘The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.
基金National Key Research and Development Program,Grant/Award Number:2017YFSF090107National Natural Science Foundation of China,Grant/Award Numbers:82072996,81874131+1 种基金Hubei Province Natural Science Funds for Distinguished Young Scholar,Grant/Award Number:2017CFA062Innovative research team of high-level local universities in Shanghai,Grant/Award Number:ZLCX20180500。
文摘Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy can ultimately relapse and progress.Thus,some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy.Recently,multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response;thus,vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes.A successful antitumor immune response requires an intact“Cancer-Immunity Cycle,”including T cell priming and activation,immune cell recruitment,and recognition and killing of cancer cells.Angiogenic inducers,especially vascular endothelial growth factor(VEGF),can interfere with activation,infiltration,and function of T cells,thus breaking the“Cancer-Immunity Cycle.”Together with immunostimulation-regulated tumor vessel remodeling,VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors.Following the successes of recent landmark phase III clinical trials,therapies combining immune checkpoint inhibitors(ICIs)with antiangiogenic agents have become first-line treatments for multiple solid tumors,whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies.In this review,we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies.Then,we discussed recent progress in randomized clinical trials.ICI-containing combinations were the focus of this review because of their recent successes,but combinations containing other immunotherapies were also discussed.Finally,we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate collaboration within the research community.
基金supported by National Natural Science Foundation of China(Grant 81600906)the Fundamental Research Funds for the Central University of China(No.2042018kf0108).
文摘Postmenopausal osteoporosis is a common chronic dynamic bone disorder,caused by estrogen deficiency.To address this issue,we constructed a controlled drug-release system composed of poly(N-isopropylacrylamide)brush modified mesoporous hydroxyapatite(MHA-SIM-P)loaded with simvastatin(SIM)using an ovariectomised(OVX)rat model.Quantitative alkaline phosphatase activity assay,alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro.The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells(BMSCs)in vitro.In osteoporotic animal model,the therapeutic efficiency for bone defect was evaluated byμCT analysis,tartrateresistant acid phosphatase,haematoxylin and eosin staining,which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks.This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis.Thus,this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.
基金supported by the National Natural Science Foundation of China(81702703)the China Postdoctoral Science Foundation(2018M630883)+1 种基金the Key Research and Development Program of Science and Technology Department of Sichuan Province(2020YFS0570,2019YFS0514,2022YFS0159,2022YFS0606)the Joint Funds of Center for Engineering Medicine of UESTC(ZYGX2021YGLH017).
文摘In a recent study published in Science,Tsvetkov et al1.shed a light on a new form of cell death,copper-dependent cell death(termed cuproptosis).They defined“cuproptosis”as a nonapoptotic cell death pathway.They have demonstrated that copper directly binds to lipoylated components of the tricarboxylic acid(TCA)cycle.Then aggregation of these copper-bound,lipoylated mitochondrial proteins and subsequent Fe-S cluster protein loss triggered proteotoxic stress and a distinct form of cell death.
基金financially supported by National Natural Science Foundation of China[Nos.82072996(Z.Sun.),81874131(Z.Sun),51703187(Z.Xu)]National Key Research and Development Program(No.2017YFSF090107)+2 种基金the Chongqing Talent Plan for Young Top Notch Talents(No.CQYC202005029)Hubei Province Natural Science Funds for Distinguished Young Scholar[No.2017CFA062(Z.Sun)]Innovative Research Team of High-level Local Universities in Shanghai[No.ZLCX20180500(Z.Sun)].
文摘Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a death mode of tumor cells that can promote tumor immunity.ICD can induce strong an-titumor immune responses through the ectopic exposure of calreticulin on the plasma membrane surface and the release of the non-histone nuclear protein high-mobility group box 1(HMGB1),ATP,and in-terferon(IFN),thus activating an adaptive immune response against dead cell-associated antigens and enhancing the therapeutic effect of tumor immunotherapy.Chemotherapy,radiotherapy,photothermal therapy,magneto-thermodynamics therapy,nanopulse stimulation,and oncolytic virus therapy can all induce a strong antitumor immune response by ICD.In addition,the application of nanotechnology can precisely target drug delivery and improve the efficacy of immunotherapy.Here we introduce the basic concepts and molecular mechanisms underlying the induction of ICD.Then,we summarize and discuss the progress in the application of nanotechnology in immunotherapy to promote ICD.Finally,we attempt to define the challenges and future directions in this area to extend the benefits of ICD to a broader patient population.
