The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understoo...The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.展开更多
Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs(miRN...Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs(miRNAs), from donors to receptors.MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b. Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1(Mcl-1) was verified as the functional target, which triggered further downstream activation of endogenous mitochondria-related apoptotic processes during tooth development.More importantly, mandible exosomes were responsible for the initial apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir-133 b resulted in failed tooth formation after 12 weeks of subcutaneous transplantation in nude mice. The tooth germ developed abnormally without the indispensable exosomal signals from the mandible.展开更多
Diphenyl carbonate(DPC)is one of the versatile carbonates,and is often used for the production of polycarbonates.In recent years,the catalytic synthesis of DPC has become an important topic but the development of a hi...Diphenyl carbonate(DPC)is one of the versatile carbonates,and is often used for the production of polycarbonates.In recent years,the catalytic synthesis of DPC has become an important topic but the development of a highly active metal-free catalyst is a great challenge.Herein,a series of ionic liquids-SBA-15 hybrid catalysts with different functional groups have been developed for the synthesis of DPC under solventfree condition,which are effective and clean instead of the metal-containing catalysts.It is found that in the presence of[SBA-15-IL-OH]Br catalyst,methyl phenyl carbonate(MPC)conversion of 80.5%along with 99.6%DPC selectivity is achieved,the TOF value is thrice higher than the best value reported by using transition metal-based catalysts.Moreover,the catalyst displays remarkable stability and recyclability.This work provides a new idea to design and prepare eco-friendly catalysts in a broad range of applications for the green synthesis of carbonates.展开更多
In this work,the removal of 2,4,6-tribromophenol(TBP)by ferric ion-activated sulfite[Fe(Ⅲ)/S(Ⅳ)]process was systematically investigated with determining the intermediate products and evaluating the influences of som...In this work,the removal of 2,4,6-tribromophenol(TBP)by ferric ion-activated sulfite[Fe(Ⅲ)/S(Ⅳ)]process was systematically investigated with determining the intermediate products and evaluating the influences of some operational conditions and water matrices.Our results show that batching addition of S(Ⅳ)benefits the S(Ⅳ)utilization efficiency and TBP removal,with SO_(4)^(-)being the primary reactive radical accounting for TBA degradation.The maximum TBP removal in the Fe(Ⅲ)/S(Ⅳ)process was observed at pH 4.0 and oxygen is essential in this process.With increasing Fe(Ⅲ)and S(Ⅳ)dosages from 0.05 and 0.1 mmol/L to 0.2 and 2.0 mmol/L,respectively,TBP removal followed trends of first increase then decrease.As the acute toxicity of the TBP solution was significantly reduced,the Fe(Ⅲ)/S(Ⅳ)process was believed to be a good choice in the treatment of TBP.展开更多
The burden of dental diseases is increasing in the Chinese population.However,the development of the dental industry falls behind the average development level of medical industry in China.The emergence of digital den...The burden of dental diseases is increasing in the Chinese population.However,the development of the dental industry falls behind the average development level of medical industry in China.The emergence of digital dental technologies has created significant opportunities for the development of the dental industry in China.This article explores the innovative development background of the Chinese dental industry,describes the current innovation status in Chinese medical colleges and enterprises,highlights key problems faced by the nation,enterprises,and hospitals,proposes solutions to these issues,and puts forwards a new concept of building an open and collaborative service system,a transformation path,and a whole-chain support system for innovations in dentistry.展开更多
Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but ...Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently,when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.展开更多
Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular...Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.展开更多
Oxidized starch powder and cationic starch solution were reacted with alkyl ketene dimer(AKD) under heterogeneous conditions at 70℃ for 12 h.The AKD molecules reacted with starch hydroxyl groups to form β-keto ester...Oxidized starch powder and cationic starch solution were reacted with alkyl ketene dimer(AKD) under heterogeneous conditions at 70℃ for 12 h.The AKD molecules reacted with starch hydroxyl groups to form β-keto ester linkages under the above conditions.The reaction products were separated into CHCl_3-soluble and CHCl_3-insoluble fractions.FT-IR spectroscopy,SEM,Xray diffraction,and TG-DTA analyses of the CHCl_3-insoluble fraction indicated that β-keto ester substituents were introduced to hydroxyl groups on the starch surfaces.The results indicated that hydrogen bonds between the starch molecules were disrupted under heterogeneous conditions upon heating.The activity and accessibility of hydroxyl groups were enhanced,as a result of which β-keto ester bonds were produced between AKD and starch.Based on these results,we speculate that the β-keto esters which existed in the sheets sized by AKD emulsions were generated by the reaction between AKD and starch.展开更多
Na Cl O has been widely used to restore membrane flux in practical membrane cleaning processes,which would induce the formation of toxic halogenated byproducts.In this study,we proposed a novel heatactivated peroxydis...Na Cl O has been widely used to restore membrane flux in practical membrane cleaning processes,which would induce the formation of toxic halogenated byproducts.In this study,we proposed a novel heatactivated peroxydisulfate(heat/PDS)process to clean the membrane fouling derived from humic acid(HA).The results show that the combination of heat and PDS can achieve almost 100%recovery of permeate flux after soaking the HA-fouled membrane in 1 mmol/L PDS solution at 50℃ for 2 h,which is attributed to the changes of HA structure and enhanced detachment of foulants from membranes.The properties of different treated membranes are characterized by scanning electron microscopy(SEM),atomic force microscope(AFM),attenuated total reflection Fourier transform infrared spectroscopy(ATRFTIR),and X-ray photoelectron spectroscopy(XPS),demonstrating that the reversible and irreversible foulants could be effectively removed by heat/PDS cleaning.The filtration process and fouling mechanism of the cleaned membrane were close to that of the virgin membrane,illustrating the good reusability of the cleaned membrane.Additionally,heat/PDS which can avoid the generation of halogenated byproducts shows comparable performance to Na Cl O on membrane cleaning and high performance for the removal of fouling caused by sodium alginate(SA),HA-bovine serum albumin(BSA)-SA mixture and algae,further suggesting that heat/PDS would be a potential alternative for membrane cleaning in practical application.展开更多
As a non-destructive testing technology,neutron imaging plays an important role in various fields,including material science,nuclear engineering,and fundamental science.An imaging detector with a neutron-sensitive ima...As a non-destructive testing technology,neutron imaging plays an important role in various fields,including material science,nuclear engineering,and fundamental science.An imaging detector with a neutron-sensitive image intensifier has been developed and demonstrated to achieve good spatial resolution and timing resolution.However,the influence of the working voltage on the performance of the neutron-sensitive imaging intensifier has not been studied.To optimize the performance of the neutron-sensitive image intensifier at different voltages,experiments have been performed at the China Spallation Neutron Source(CSNS)neutron beamline.The change in the light yield and imaging quality with different voltages has been acquired.It is shown that the image quality benefits from the high gain of the microchannel plate(MCP)and the high accelerating electric field between the MCP and the screen.Increasing the accelerating electric field is more effective than increasing the gain of MCPs for the improvement of the imaging quality.Increasing the total gain of the MCP stack can be realized more effectively by improving the gain of the standard MCP than that of the n MCP.These results offer a development direction for image intensifiers in the future.展开更多
This study focuses on the application of the“PBL(problem-based learning)+Flipped Classroom”teaching model in bilingual education,aiming to explore its potential to enhance the quality and effectiveness of bilingual ...This study focuses on the application of the“PBL(problem-based learning)+Flipped Classroom”teaching model in bilingual education,aiming to explore its potential to enhance the quality and effectiveness of bilingual teaching.PBL emphasizes learning through the resolution of real-world problems,while the Flipped Classroom advocates that students acquire basic knowledge through self-study before class,dedicating class time to in-depth discussions and practical activities.The integration of these two teaching models in bilingual education aims to stimulate students’interest in learning,improve their autonomous learning abilities,enhance critical thinking,and foster cross-cultural communication skills.Through literature review,case analysis,and empirical research,this study first examines the current applications and challenges of PBL and the Flipped Classroom in bilingual education.Subsequently,it elaborates on the specific implementation steps of the“PBL+Flipped Classroom”teaching model in bilingual education,including problem design,preview material provision,cooperative learning,classroom activities,and language support.A comparative experiment is then conducted to analyze the impact of this teaching model on students’learning motivation,academic performance,and cross-cultural communication skills.The results indicate that the“PBL+Flipped Classroom”teaching model significantly improves students’learning motivation and participation,enhances academic performance,and effectively boosts their cross-cultural communication skills.Furthermore,this model aids in cultivating students’autonomous learning abilities and critical thinking,providing an innovative and effective approach to bilingual education.This study offers new ideas and insights for the field of bilingual education,which is of great significance for promoting the innovation and development of bilingual teaching models.展开更多
Atherosclerosis is characterized by abnormal lipid metabolism,leading to the accumulation of lipids beneath the endothelium of large arteries and the gradual formation of plaques.Unstable plaques can trigger major car...Atherosclerosis is characterized by abnormal lipid metabolism,leading to the accumulation of lipids beneath the endothelium of large arteries and the gradual formation of plaques.Unstable plaques can trigger major cardiovascular events.Although nitrate is known for its cardiovascular protective effects,such as lowering blood pressure and preventing vascular endothelial damage,its role in preventing atherosclerosis remains uncertain.This study demonstrates through animal experiments that nitrate can prevent the formation of aortic plaques induced by a high-fat diet in ApoE^(-/-)mice.RNA sequencing data from the aortic arch indicated that nitrate administration reduced the expression of inflammatory factors within the vessel walls and improved the immunological microenvironment of the aorta.Moreover,in vitro experiments revealed that nitrate decreases the expression of Lox-1 and IL-1β,thereby reducing the formation and apoptosis of foam cells derived from M2 macrophages by maintaining their homeostasis,which is beneficial in mitigating early plaque development.Lox-1 overexpression experiments demonstrated that the biological effects of nitrate are dependent on the Lox-1 molecule.Further validation through Transwell?assays demonstrated that nitrate decreased the expression of MCP1,ICAM1,and VCAM1 in vascular endothelial cells,thereby reducing the adhesion of macrophages.In summary,nitrate ameliorated atherosclerosis by maintaining the homeostasis of M2 macrophages,reducing their apoptosis,local inflammation within plaques,and macrophage adhesion,ultimately leading to reduced plaque formation in the aortas of ApoE^(-/-)mice.展开更多
Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by cognitive decline.The pathological hallmarks of AD include the deposition of b-amyloid(Ab)plaques,hyperphosphorylation of tau protei...Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by cognitive decline.The pathological hallmarks of AD include the deposition of b-amyloid(Ab)plaques,hyperphosphorylation of tau protein,synaptic loss,and reactive astrogliosis in the brain[1].As there is still no effective therapy for AD,the development of novel treatment strategies is imperative.展开更多
Metabolic syndrome,characterized by metabolic dysfunction-associated steatotic liver disease(MASLD)and type 2 diabetes mellitus(T2DM),poses a significant threat to patients'health worldwide;however,efficient treat...Metabolic syndrome,characterized by metabolic dysfunction-associated steatotic liver disease(MASLD)and type 2 diabetes mellitus(T2DM),poses a significant threat to patients'health worldwide;however,efficient treatment is currently unavailable.Here,we show that oral administration of sodium nitrate(NaNO3)greatly attenuates the development and advancement of MASLD-like and T2DM-like phenotypes in mice induced by choline-deficient high-fat,western,or methionine/choline-deficient diet.NaNO3 attenuates metabolic turbulence by rebalancing CD206+/CD11C+polarization(anti-inflammatory/pro-inflammatory)and the function of bone marrow-derived macrophages(MoMFs).Using metabolic disorder animal models and bone marrow-reconstituted mice with mutated gene function in Slc17a5,which encodes sialin,we demonstrate that NaNO3 protects against metabolic disorders through the actions of sialin in MoMFs.NaNO3 can directly regulate MoMFs polarization and function in vitro and in mice,in which nitric oxide production from oral and enteral symbiotic bacteria is essentially abolished.At the molecular level,sialin,via the inhibition of the key transcription factor Rel,inhibits cathepsin L(CtsL)expression and thereby activates the Nrf2 pathway to modulate macrophage homeostasis and ameliorate metabolic abnormalities.Interestingly,the sialin-CtsL-Nrf2 pathway is downregulated in human macrophages from metabolic dysfunction-associated steatohepatitis(MASH)patients.Overall,we demonstrate the prophylactic and therapeutic effects of NaNO3 on metabolic syndrome and reveal a new macrophage rebalancing strategy involving NaNO3 through a novel sialin pathway.Our research indicates that NaNO3 may be a pharmaceutical agent for managing and alleviating metabolic turbulence in humans.展开更多
Hepatic ischemia–reperfusion injury(HIRI)is an important cause of liver injury following liver transplantation and major resections,and neutrophils are the key effector cells in HIRI.Double-negative T regulatory cell...Hepatic ischemia–reperfusion injury(HIRI)is an important cause of liver injury following liver transplantation and major resections,and neutrophils are the key effector cells in HIRI.Double-negative T regulatory cells(DNT)are increasingly recognized as having critical regulatory functions in the immune system.Whether DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils,as in HIRI,remains largely unknown.In this study,we found that murine and human DNT highly expressed CD39that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73,to induce high levels of neutrophil apoptosis.Furthermore,extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling pathway.Adoptive transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent manner.Lastly,the adoptive transfer of A2ar^(-/-)DNT validated the importance of adenosine/A2AR signaling,in promoting DNT survival and immunomodulatory function to protect against HIRI in vivo.In conclusion,purinergic signaling is crucial for DNT homeostasis in HIRI.Augmentation of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders.展开更多
Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma(OSCC)treatment,it exerts multiple side effects and poor chemosensitivity.Nitrate reportedly demonstrates several ...Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma(OSCC)treatment,it exerts multiple side effects and poor chemosensitivity.Nitrate reportedly demonstrates several beneficial biological functions,and synthesized nitrates enhance the therapeutic efficacy of chemotherapy.However,the role of inorganic nitrate in cisplatin chemotherapy remains unclear.We therefore investigated the effect of inorganic nitrate exerted on cisplatin sensitivity in OSCC.We found that nitrate did not affect OSCC cell growth and apoptosis in OSCC cells and OSCC xenograft tumor animal studies.Cisplatin induced REDD1 expression and AKT activation in OSCC.However,nitrate could increase cisplatin chemosensitivity,reduce its REDD1 expression,and attenuate AKT signaling activation in OSCC cells.Dysregulation of high levels of REDD1,which could enhance AKT activation,was positively associated with poor prognosis in OSCC patients.Thus,reduced REDD1 expression and retarded AKT activation induced by inorganic nitrate might be a new potential approach to the sensitization of oral cancer to cisplatin treatment in the future.展开更多
The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in humans.The human gingiva ...The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in humans.The human gingiva exists as a complex cell network comprising specialized structures.To understand the tissue-specific pathophysiology of the gingiva,we applied a recently developed spatial enhanced resolution omics-sequencing(Stereo-seq)technique to obtain a spatial transcriptome(ST)atlas of the gingiva in healthy individuals and periodontitis patients.By utilizing Stereo-seq,we identified the major cell types present in the gingiva,which included epithelial cells,fibroblasts,endothelial cells,and immune cells,as well as subgroups of epithelial cells and immune cells.We further observed that inflammation-related signalling pathways,such as the JAK-STAT and NF-κB signalling pathways,were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals.Additionally,we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva.In conclusion,our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.展开更多
Cellular senescence affects the efficacy of mesenchymal stem cells(MSCs)-mediated tissue regeneration.Insulin-like growth factor binding proteins-7(IGFBP7),as a member of the IGF family,is associated with osteogenic d...Cellular senescence affects the efficacy of mesenchymal stem cells(MSCs)-mediated tissue regeneration.Insulin-like growth factor binding proteins-7(IGFBP7),as a member of the IGF family,is associated with osteogenic differentiation and the senescence of MSCs,but its exact function and mechanism remain unclear.We found IGFBP7 promoted the osteogenic differentiation and prevented the senescence of dental pulp-derived MSCs(DPSCs),as observed in the gain-of-function and lossof-function analyses,the senescence-associated marker p21 showed the most pronounced expression changes.We demonstrated that IGFBP7 activated the biological activity of SIRT1 deacetylase via metabolism,resulting in a deacetylation of H3K36ac and a decrease of the binding affinity of H3K36ac to p21 promoter,thereby reducing the transcription of p21,which ultimately prevents DPSCs senescence and promotes tissue regeneration.The activation of the mitochondrial electron transport chain(ETC)by Coenzyme Q10 could rescue the promotion of DPSC senescence induced by the knockdown of IGFBP7,whereas the inhibition of ETC by rotenone attenuated the prevention of DPSC senescence induced by IGFBP7 overexpression.In conclusion,our present results reveal a novel function of IGFBP7 in preventing DPSC senescence via the metabolism-induced deacetylation of H3K36ac and reduction of p21 transcription,suggesting that IGFBP7 is a potential target for promoting tissue regeneration in an aging environment.展开更多
Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals.Dietary nitrate supplements have physiological and therapeutic effects on orga...Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals.Dietary nitrate supplements have physiological and therapeutic effects on organ function by nitrate(NO_3^-)-nitrite(NO_2^-)-nitric oxide(NO)pathway.However,the role of dietary nitrate on the senescence-related decline in liver function is unclear.The findings of the present study showed that nitrate levels in the serum and liver decreased,whereas the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum increased in ageing mice.Consistently,cell senescence,decreased glycogen levels and increased lipid deposition were found in the liver of aged mice,both glucokinase(GCK)and phosphoenolpyruvate carboxykinase(PCK)were down-regulated(n=10).Daily nitrate intake(0.5 mmol L^(-1))restored nitrate levels,decreased ALT and AST levels,and prevented cell senescence and structural and glucose and lipid metabolism degeneration in liver tissue both in D-galactose(D-gal)-induced ageing mice(n=10)and in natural aged mice(n=10).In conclusion,the present study demonstrated that the reduction of nitrate levels was correlated with liver degeneration in ageing individuals and that dietary supplement of nitrate could restore the nitrate levels in serum and the liver and prevent ageing-related liver degeneration.展开更多
基金supported by the National Key Research and Development Program(2022YFA1104401)Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+3 种基金Beijing Municipal Govemment(Beijing Scholar Program,PXM2021-014226-000020)National Natural Science Foundation of China(82030031,92149301,81991504,L2224038,82270945)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5-031).
文摘The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
基金supported by the National Natural Science Foundation of China (No. 91649124 to S.W. No. 81371108 and 81670955 to A.L. and No. 81701037 to Y.L.)+1 种基金Beijing Municipality Government grants (Beijing Scholar ProgramPXM2016_014226_000006, PXM2016_014226_000034, PXM2015_014226_000052, PXM2015_014226_000055, PXM2015_014226_000116, PXM2014_014226_000013, PXM2014_014226_000048, PXM2014_014226_000053, Z121100005212004, PXM2013_014226_000021, PXM2013_014226_000055, PXM 2013_014226_07_ 000080 and TJSHG201310025005 to S.W.)an Open grant from Capital Medical University (No. KFKT2016005 to Y.L.)
文摘Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs(miRNAs), from donors to receptors.MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b. Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1(Mcl-1) was verified as the functional target, which triggered further downstream activation of endogenous mitochondria-related apoptotic processes during tooth development.More importantly, mandible exosomes were responsible for the initial apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir-133 b resulted in failed tooth formation after 12 weeks of subcutaneous transplantation in nude mice. The tooth germ developed abnormally without the indispensable exosomal signals from the mandible.
基金support from the National Natural Science Foundation of China(No.21808048 and U1704251)Training Plan for University's Young Backbone Teachers of Henan Province(2021GGJS121)+5 种基金Program for Science&Technology Innovation Talents in Universities of Henan Province(23HASTIT014)Postgraduate Education Reform and Quality Improvement Project of Henan Province(YJS2022KC22)Project funded by China Postdoctoral Science Foundation(No.2018M632782)Project funded by Postdoctoral Research Grant in Henan Province(No.001802030)Key Project of Science and Technology Program of Henan Province(No.222102230109,212102310330 and 182102210050)the Science Research Start-up Fund of Henan Institute of Science and Technology(No.2015031).
文摘Diphenyl carbonate(DPC)is one of the versatile carbonates,and is often used for the production of polycarbonates.In recent years,the catalytic synthesis of DPC has become an important topic but the development of a highly active metal-free catalyst is a great challenge.Herein,a series of ionic liquids-SBA-15 hybrid catalysts with different functional groups have been developed for the synthesis of DPC under solventfree condition,which are effective and clean instead of the metal-containing catalysts.It is found that in the presence of[SBA-15-IL-OH]Br catalyst,methyl phenyl carbonate(MPC)conversion of 80.5%along with 99.6%DPC selectivity is achieved,the TOF value is thrice higher than the best value reported by using transition metal-based catalysts.Moreover,the catalyst displays remarkable stability and recyclability.This work provides a new idea to design and prepare eco-friendly catalysts in a broad range of applications for the green synthesis of carbonates.
基金The support by the National Natural Science Foundation of China(No.51878308)the Young Top-notch Talent Cultivation Program of Hubei Province。
文摘In this work,the removal of 2,4,6-tribromophenol(TBP)by ferric ion-activated sulfite[Fe(Ⅲ)/S(Ⅳ)]process was systematically investigated with determining the intermediate products and evaluating the influences of some operational conditions and water matrices.Our results show that batching addition of S(Ⅳ)benefits the S(Ⅳ)utilization efficiency and TBP removal,with SO_(4)^(-)being the primary reactive radical accounting for TBA degradation.The maximum TBP removal in the Fe(Ⅲ)/S(Ⅳ)process was observed at pH 4.0 and oxygen is essential in this process.With increasing Fe(Ⅲ)and S(Ⅳ)dosages from 0.05 and 0.1 mmol/L to 0.2 and 2.0 mmol/L,respectively,TBP removal followed trends of first increase then decrease.As the acute toxicity of the TBP solution was significantly reduced,the Fe(Ⅲ)/S(Ⅳ)process was believed to be a good choice in the treatment of TBP.
文摘The burden of dental diseases is increasing in the Chinese population.However,the development of the dental industry falls behind the average development level of medical industry in China.The emergence of digital dental technologies has created significant opportunities for the development of the dental industry in China.This article explores the innovative development background of the Chinese dental industry,describes the current innovation status in Chinese medical colleges and enterprises,highlights key problems faced by the nation,enterprises,and hospitals,proposes solutions to these issues,and puts forwards a new concept of building an open and collaborative service system,a transformation path,and a whole-chain support system for innovations in dentistry.
基金supported by the grants from the National Natural Science Foundation of China(81970922 to J.X.and 81771055 to C.L.)。
文摘Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently,when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
基金the National Natural Science Foundation of China(82030031,L2224038,92149301)Chinese Academy of Medical Sciences Research Unit(2019-12M-5-031)+4 种基金Beijing Municipal Science&Technology Commission(Z181100001718208)Beijing Municipal Education Commission(119207020201)Beijing Municipality Government Grants(Beijing Laboratory of Oral Health-PXM2021_014226_000041,Beijing Scholar Program-PXM2021_014226_000020)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Young Scientist Program of Beijing Stomatological Hospital,Capital Medical University(YSP202308).
文摘Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.
基金financial support from Shandong Province Education Department(Grant No.J14 LC11)National Natural Science Foundation of China(Grant No.21406126 and 21576146)+2 种基金Department of Science and Technology of Shandong Province(Grant No.2014 GSF116001)973(Grant No.2014 CB460610)Department of Science and Technology of Shandong Province(Grant No.2015 ZDXX0403 B03)
文摘Oxidized starch powder and cationic starch solution were reacted with alkyl ketene dimer(AKD) under heterogeneous conditions at 70℃ for 12 h.The AKD molecules reacted with starch hydroxyl groups to form β-keto ester linkages under the above conditions.The reaction products were separated into CHCl_3-soluble and CHCl_3-insoluble fractions.FT-IR spectroscopy,SEM,Xray diffraction,and TG-DTA analyses of the CHCl_3-insoluble fraction indicated that β-keto ester substituents were introduced to hydroxyl groups on the starch surfaces.The results indicated that hydrogen bonds between the starch molecules were disrupted under heterogeneous conditions upon heating.The activity and accessibility of hydroxyl groups were enhanced,as a result of which β-keto ester bonds were produced between AKD and starch.Based on these results,we speculate that the β-keto esters which existed in the sheets sized by AKD emulsions were generated by the reaction between AKD and starch.
基金supported by the Natural Science Foundation of China(Nos.52070081,51578258 and 51878308)the National Key Research and Development Program of China(No.2022YFC3203500)。
文摘Na Cl O has been widely used to restore membrane flux in practical membrane cleaning processes,which would induce the formation of toxic halogenated byproducts.In this study,we proposed a novel heatactivated peroxydisulfate(heat/PDS)process to clean the membrane fouling derived from humic acid(HA).The results show that the combination of heat and PDS can achieve almost 100%recovery of permeate flux after soaking the HA-fouled membrane in 1 mmol/L PDS solution at 50℃ for 2 h,which is attributed to the changes of HA structure and enhanced detachment of foulants from membranes.The properties of different treated membranes are characterized by scanning electron microscopy(SEM),atomic force microscope(AFM),attenuated total reflection Fourier transform infrared spectroscopy(ATRFTIR),and X-ray photoelectron spectroscopy(XPS),demonstrating that the reversible and irreversible foulants could be effectively removed by heat/PDS cleaning.The filtration process and fouling mechanism of the cleaned membrane were close to that of the virgin membrane,illustrating the good reusability of the cleaned membrane.Additionally,heat/PDS which can avoid the generation of halogenated byproducts shows comparable performance to Na Cl O on membrane cleaning and high performance for the removal of fouling caused by sodium alginate(SA),HA-bovine serum albumin(BSA)-SA mixture and algae,further suggesting that heat/PDS would be a potential alternative for membrane cleaning in practical application.
基金Project supported by the National Key R&D Program of China (Grant Nos.2023YFC2206502 and 2021YFA1600703)the National Natural Science Foundation of China (Grant Nos.12175254 and 12227810)the Guangdong–Hong Kong–Macao Joint Laboratory for Neutron Scattering Science and Technology。
文摘As a non-destructive testing technology,neutron imaging plays an important role in various fields,including material science,nuclear engineering,and fundamental science.An imaging detector with a neutron-sensitive image intensifier has been developed and demonstrated to achieve good spatial resolution and timing resolution.However,the influence of the working voltage on the performance of the neutron-sensitive imaging intensifier has not been studied.To optimize the performance of the neutron-sensitive image intensifier at different voltages,experiments have been performed at the China Spallation Neutron Source(CSNS)neutron beamline.The change in the light yield and imaging quality with different voltages has been acquired.It is shown that the image quality benefits from the high gain of the microchannel plate(MCP)and the high accelerating electric field between the MCP and the screen.Increasing the accelerating electric field is more effective than increasing the gain of MCPs for the improvement of the imaging quality.Increasing the total gain of the MCP stack can be realized more effectively by improving the gain of the standard MCP than that of the n MCP.These results offer a development direction for image intensifiers in the future.
基金Quality Engineering Project of Chuzhou University“A Study on the Application of the‘PBL+Flipped Classroom’Teaching Mode Integrated with Rain Classroom in Bilingual Teaching of International Enterprise Management”(2022jyc047)Scientific Research Projects of Higher Education Institutions in Anhui Province“Research on the Mechanism of Enabling the Dual-Chain Integration of‘Industry Chain–Talent Chain’in Anhui through New Quality Productivity”(2024AH052932)+1 种基金Education Science Planning Project of Jiangsu Province“Research on the Reform of Practical Teaching in Open Universities under Digital Transformation”(C/2023/01/126)Project of Social Science Foundation of Jiangsu Province“Research on the Path and Mechanism of Digital Empowerment for the Integration of‘Industry Chain-Talent Chain’in Jiangsu”(23GLD002)。
文摘This study focuses on the application of the“PBL(problem-based learning)+Flipped Classroom”teaching model in bilingual education,aiming to explore its potential to enhance the quality and effectiveness of bilingual teaching.PBL emphasizes learning through the resolution of real-world problems,while the Flipped Classroom advocates that students acquire basic knowledge through self-study before class,dedicating class time to in-depth discussions and practical activities.The integration of these two teaching models in bilingual education aims to stimulate students’interest in learning,improve their autonomous learning abilities,enhance critical thinking,and foster cross-cultural communication skills.Through literature review,case analysis,and empirical research,this study first examines the current applications and challenges of PBL and the Flipped Classroom in bilingual education.Subsequently,it elaborates on the specific implementation steps of the“PBL+Flipped Classroom”teaching model in bilingual education,including problem design,preview material provision,cooperative learning,classroom activities,and language support.A comparative experiment is then conducted to analyze the impact of this teaching model on students’learning motivation,academic performance,and cross-cultural communication skills.The results indicate that the“PBL+Flipped Classroom”teaching model significantly improves students’learning motivation and participation,enhances academic performance,and effectively boosts their cross-cultural communication skills.Furthermore,this model aids in cultivating students’autonomous learning abilities and critical thinking,providing an innovative and effective approach to bilingual education.This study offers new ideas and insights for the field of bilingual education,which is of great significance for promoting the innovation and development of bilingual teaching models.
基金supported by the Beijing Municipality Government Grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)the Beijing Municipality Government Grant(Beijing Scholar Program,PXM2021-014226-000020)+5 种基金the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)the Chinese Research Unit of Tooth Development and RegenerationChinese Academy of Medical Sciences(2019-12M-5-031)the National Natural Science Foundation of China(82030031,82170951,82470961,81741106,82201054)the State Key Laboratory of Oral DiseasesSichuan University(SKLOD2023OF13).
文摘Atherosclerosis is characterized by abnormal lipid metabolism,leading to the accumulation of lipids beneath the endothelium of large arteries and the gradual formation of plaques.Unstable plaques can trigger major cardiovascular events.Although nitrate is known for its cardiovascular protective effects,such as lowering blood pressure and preventing vascular endothelial damage,its role in preventing atherosclerosis remains uncertain.This study demonstrates through animal experiments that nitrate can prevent the formation of aortic plaques induced by a high-fat diet in ApoE^(-/-)mice.RNA sequencing data from the aortic arch indicated that nitrate administration reduced the expression of inflammatory factors within the vessel walls and improved the immunological microenvironment of the aorta.Moreover,in vitro experiments revealed that nitrate decreases the expression of Lox-1 and IL-1β,thereby reducing the formation and apoptosis of foam cells derived from M2 macrophages by maintaining their homeostasis,which is beneficial in mitigating early plaque development.Lox-1 overexpression experiments demonstrated that the biological effects of nitrate are dependent on the Lox-1 molecule.Further validation through Transwell?assays demonstrated that nitrate decreased the expression of MCP1,ICAM1,and VCAM1 in vascular endothelial cells,thereby reducing the adhesion of macrophages.In summary,nitrate ameliorated atherosclerosis by maintaining the homeostasis of M2 macrophages,reducing their apoptosis,local inflammation within plaques,and macrophage adhesion,ultimately leading to reduced plaque formation in the aortas of ApoE^(-/-)mice.
基金supported by the National Natural Science Foundation of China(82030031,91649124,and 92049201)Beijing Municipal Science&Technology Commission(Z181100001718208)+8 种基金Chinese Academy of Medical Sciences Research Unit(2019–12M-5-031)Beijing Municipality Government grants(Beijing Laboratory of Oral HealthPXM2021_014226_000041Beijing Scholar ProgramPXM2021_014226_000021)Beijing Municipal Education Commission(119207020201)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Scientific Research Common Program of Beijing Municipal Commission of Education(KM202110025009)Beijing Municipal Natural Science Foundation(7232071)Scientific Research Key Program of Beijing Municipal Commission of Education(KZ202110025032)the STI2030-Major Project(2021ZD0201100 Task 1-2021ZD0201101).
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by cognitive decline.The pathological hallmarks of AD include the deposition of b-amyloid(Ab)plaques,hyperphosphorylation of tau protein,synaptic loss,and reactive astrogliosis in the brain[1].As there is still no effective therapy for AD,the development of novel treatment strategies is imperative.
基金funding by the National Natural Science Foundation of China(82201054,82030031,L2224038)the Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+4 种基金the Beijing Municipal Science and Technology Commission(Z181100001718208)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(YSP202102)the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)the Beijing Municipal Government(Beijing Scholar Program,PXM2020_014226_000005 and PXM2021_014226_000020)State Key Laboratory of Oral Diseases,Sichuan University(SKLOD2023OF13)。
文摘Metabolic syndrome,characterized by metabolic dysfunction-associated steatotic liver disease(MASLD)and type 2 diabetes mellitus(T2DM),poses a significant threat to patients'health worldwide;however,efficient treatment is currently unavailable.Here,we show that oral administration of sodium nitrate(NaNO3)greatly attenuates the development and advancement of MASLD-like and T2DM-like phenotypes in mice induced by choline-deficient high-fat,western,or methionine/choline-deficient diet.NaNO3 attenuates metabolic turbulence by rebalancing CD206+/CD11C+polarization(anti-inflammatory/pro-inflammatory)and the function of bone marrow-derived macrophages(MoMFs).Using metabolic disorder animal models and bone marrow-reconstituted mice with mutated gene function in Slc17a5,which encodes sialin,we demonstrate that NaNO3 protects against metabolic disorders through the actions of sialin in MoMFs.NaNO3 can directly regulate MoMFs polarization and function in vitro and in mice,in which nitric oxide production from oral and enteral symbiotic bacteria is essentially abolished.At the molecular level,sialin,via the inhibition of the key transcription factor Rel,inhibits cathepsin L(CtsL)expression and thereby activates the Nrf2 pathway to modulate macrophage homeostasis and ameliorate metabolic abnormalities.Interestingly,the sialin-CtsL-Nrf2 pathway is downregulated in human macrophages from metabolic dysfunction-associated steatohepatitis(MASH)patients.Overall,we demonstrate the prophylactic and therapeutic effects of NaNO3 on metabolic syndrome and reveal a new macrophage rebalancing strategy involving NaNO3 through a novel sialin pathway.Our research indicates that NaNO3 may be a pharmaceutical agent for managing and alleviating metabolic turbulence in humans.
基金supported by the grants from the National Natural Science Foundation of China(81970503,82100670,82202021and 82270606)Chinese Institutes for Medical Research+7 种基金Beijing(CX24PY16)R&D Program of Beijing Municipal Education Commission(KZ202210025036)Beijing Municipal Administration of Hospitals’Ascent Plan(DFL20220103)Beijing Nova Program(Z211100002121036)Youth Beijing Scholar(035)and the Reform and Development Program of Beijing Institute of Respiratory Medicine(Ggyfz202403)Generation of reagents and mutant mice are also supported by the National Institutes of Health(R01 DK108894R21 CA164970 and R21 CA221702)Department of Defense Award W81XWH-16-0464。
文摘Hepatic ischemia–reperfusion injury(HIRI)is an important cause of liver injury following liver transplantation and major resections,and neutrophils are the key effector cells in HIRI.Double-negative T regulatory cells(DNT)are increasingly recognized as having critical regulatory functions in the immune system.Whether DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils,as in HIRI,remains largely unknown.In this study,we found that murine and human DNT highly expressed CD39that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73,to induce high levels of neutrophil apoptosis.Furthermore,extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling pathway.Adoptive transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent manner.Lastly,the adoptive transfer of A2ar^(-/-)DNT validated the importance of adenosine/A2AR signaling,in promoting DNT survival and immunomodulatory function to protect against HIRI in vivo.In conclusion,purinergic signaling is crucial for DNT homeostasis in HIRI.Augmentation of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders.
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-031)Beijing Hospitals Authority of Hospitals’Mission Plan(SML20151401,Capital Medical University)+1 种基金Beijing Municipality Government grants(Beijing Scholar Program—PXM2020_014226_000005,PXM2019_014226_000039,PXM2019_014226_000011,PXM2018_014226_000021,PXM2017_014226_000023,PXM2018_193312_000006_0028S643_FCG,PXM2016_014226_000034)the National Natural Science Foundation of China(91649124).
文摘Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma(OSCC)treatment,it exerts multiple side effects and poor chemosensitivity.Nitrate reportedly demonstrates several beneficial biological functions,and synthesized nitrates enhance the therapeutic efficacy of chemotherapy.However,the role of inorganic nitrate in cisplatin chemotherapy remains unclear.We therefore investigated the effect of inorganic nitrate exerted on cisplatin sensitivity in OSCC.We found that nitrate did not affect OSCC cell growth and apoptosis in OSCC cells and OSCC xenograft tumor animal studies.Cisplatin induced REDD1 expression and AKT activation in OSCC.However,nitrate could increase cisplatin chemosensitivity,reduce its REDD1 expression,and attenuate AKT signaling activation in OSCC cells.Dysregulation of high levels of REDD1,which could enhance AKT activation,was positively associated with poor prognosis in OSCC patients.Thus,reduced REDD1 expression and retarded AKT activation induced by inorganic nitrate might be a new potential approach to the sensitization of oral cancer to cisplatin treatment in the future.
基金supported by the National Natural Science Foundation of China(82201011,82030031,92149301 and 82270945)the Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+2 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-038)the Science and Technology Project of Guangzhou,China(202206080009)the Postdoctoral Foundation of China(2021M703695 and 2021TQ0308)。
文摘The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in humans.The human gingiva exists as a complex cell network comprising specialized structures.To understand the tissue-specific pathophysiology of the gingiva,we applied a recently developed spatial enhanced resolution omics-sequencing(Stereo-seq)technique to obtain a spatial transcriptome(ST)atlas of the gingiva in healthy individuals and periodontitis patients.By utilizing Stereo-seq,we identified the major cell types present in the gingiva,which included epithelial cells,fibroblasts,endothelial cells,and immune cells,as well as subgroups of epithelial cells and immune cells.We further observed that inflammation-related signalling pathways,such as the JAK-STAT and NF-κB signalling pathways,were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals.Additionally,we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva.In conclusion,our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.
基金the National Natural Science Foundation of China(82030031,81991504,92149301,82001067)the Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5-031)+7 种基金the Beijing Municipal Science and Technology Commission(Z181100001718208)the Beijing Municipal Education Commission(119207020201)Beijing Advanced Innovation Center for Big Data-based Precision Medicine(PXM2021_014226_000026)the Beijing Municipal Government(Beijing Scholar program PXM2020_014226_000005,PXM2021_014226_000020)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Beijing Municipal Administration of Hospitals’Youth Program(QML20191504)Scientific Research Common Program of Beijing Municipal Commission of Education(KM202110025009)Beijing Talents Fund(2018000021469G285)。
文摘Cellular senescence affects the efficacy of mesenchymal stem cells(MSCs)-mediated tissue regeneration.Insulin-like growth factor binding proteins-7(IGFBP7),as a member of the IGF family,is associated with osteogenic differentiation and the senescence of MSCs,but its exact function and mechanism remain unclear.We found IGFBP7 promoted the osteogenic differentiation and prevented the senescence of dental pulp-derived MSCs(DPSCs),as observed in the gain-of-function and lossof-function analyses,the senescence-associated marker p21 showed the most pronounced expression changes.We demonstrated that IGFBP7 activated the biological activity of SIRT1 deacetylase via metabolism,resulting in a deacetylation of H3K36ac and a decrease of the binding affinity of H3K36ac to p21 promoter,thereby reducing the transcription of p21,which ultimately prevents DPSCs senescence and promotes tissue regeneration.The activation of the mitochondrial electron transport chain(ETC)by Coenzyme Q10 could rescue the promotion of DPSC senescence induced by the knockdown of IGFBP7,whereas the inhibition of ETC by rotenone attenuated the prevention of DPSC senescence induced by IGFBP7 overexpression.In conclusion,our present results reveal a novel function of IGFBP7 in preventing DPSC senescence via the metabolism-induced deacetylation of H3K36ac and reduction of p21 transcription,suggesting that IGFBP7 is a potential target for promoting tissue regeneration in an aging environment.
基金supported by the National Natural Science Foundation of China (91649124)Beijing Municipality Government grants (Beijing Scholar Program- PXM2016_014226_000034, PXM2016_014226_000006, PXM2015_014226_000116, PXM2015_ 014226_000055, PXM2015_014226_000052, PXM2014_014226_000048, PXM2014_014226_000013, PXM2014_014226_000053, Z121100005212004, PXM2013_014226_000055, PXM2013_014226_000021, PXM 2013_014226_07_000080, TJSHG201310025005)
文摘Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals.Dietary nitrate supplements have physiological and therapeutic effects on organ function by nitrate(NO_3^-)-nitrite(NO_2^-)-nitric oxide(NO)pathway.However,the role of dietary nitrate on the senescence-related decline in liver function is unclear.The findings of the present study showed that nitrate levels in the serum and liver decreased,whereas the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum increased in ageing mice.Consistently,cell senescence,decreased glycogen levels and increased lipid deposition were found in the liver of aged mice,both glucokinase(GCK)and phosphoenolpyruvate carboxykinase(PCK)were down-regulated(n=10).Daily nitrate intake(0.5 mmol L^(-1))restored nitrate levels,decreased ALT and AST levels,and prevented cell senescence and structural and glucose and lipid metabolism degeneration in liver tissue both in D-galactose(D-gal)-induced ageing mice(n=10)and in natural aged mice(n=10).In conclusion,the present study demonstrated that the reduction of nitrate levels was correlated with liver degeneration in ageing individuals and that dietary supplement of nitrate could restore the nitrate levels in serum and the liver and prevent ageing-related liver degeneration.
