A clear definition of 3-D wave crest and a description of the procedures to detect the boundary of wave crest are presented in the paper. By using random wave theory and directional wave spectrum, a MATLAB-platformed ...A clear definition of 3-D wave crest and a description of the procedures to detect the boundary of wave crest are presented in the paper. By using random wave theory and directional wave spectrum, a MATLAB-platformed program is designed to simulate random wave crests for various directional spectral conditions in deep water. Statistics of wave crests with different directional spreading parameters and different directional functions are obtained and discussed.展开更多
The critically endangered Chinese Crested Tern(CThalasseus bernsteini,CCT)and its common flocking companion,the Greater Crested Tern(Thalasseus bergii,GCT),have been the focus of targeted recovery efforts in the Jiush...The critically endangered Chinese Crested Tern(CThalasseus bernsteini,CCT)and its common flocking companion,the Greater Crested Tern(Thalasseus bergii,GCT),have been the focus of targeted recovery efforts in the Jiushan Archipelago of Zhejiang Province,China since 2013.To evaluate the long-term effectiveness of these measures and address key knowledge gaps in population dynamics and migration ecology,we analyzed ten years(2015-2024)of banding and citizen science data,comprising 116 CCT and 3501 GCT resighting records.We estimated survival rates using both directly derived survival rate(based on resighting rate after two years)and Cormack-Jolly-Seber modeling,and examined migration connectivity and climate risks.Results showed robust juvenile survival:modeled survival for the tern chick population was lower in the first two years(63.9±12.0%)but exceeded 78%thereafter.This was also supported by resighting rate after two years:CCT 77.27%,GCT70.42%.A key divergence in post-breeding migration was identified:CCT moves northward to stopover sites such as Nantong,Rizhao,and Jiaozhou Bay,whereas GCT migrates southward.Climate data confirmed that northern stopover sites do not pose higher storm risks,indicating that CCT's northward migration is not a population liability.Furthermore,connectivity among breeding islands in Zhejiang and the Matsu Archipelago reveals a nascent coastal breeding network along China's coast.These findings underscore the importance of protecting both the northern migration route and the breeding island network to ensure full life-cycle conservation of CCT.展开更多
Optimization problems are prevalent in various fields of science and engineering,with several real-world applications characterized by high dimensionality and complex search landscapes.Starfish optimization algorithm(...Optimization problems are prevalent in various fields of science and engineering,with several real-world applications characterized by high dimensionality and complex search landscapes.Starfish optimization algorithm(SFOA)is a recently optimizer inspired by swarm intelligence,which is effective for numerical optimization,but it may encounter premature and local convergence for complex optimization problems.To address these challenges,this paper proposes the multi-strategy enhanced crested porcupine-starfish optimization algorithm(MCPSFOA).The core innovation of MCPSFOA lies in employing a hybrid strategy to improve SFOA,which integrates the exploratory mechanisms of SFOA with the diverse search capacity of the Crested Porcupine Optimizer(CPO).This synergy enhances MCPSFOA’s ability to navigate complex and multimodal search spaces.To further prevent premature convergence,MCPSFOA incorporates Lévy flight,leveraging its characteristic long and short jump patterns to enable large-scale exploration and escape from local optima.Subsequently,Gaussian mutation is applied for precise solution tuning,introducing controlled perturbations that enhance accuracy and mitigate the risk of insufficient exploitation.Notably,the population diversity enhancement mechanism periodically identifies and resets stagnant individuals,thereby consistently revitalizing population variety throughout the optimization process.MCPSFOA is rigorously evaluated on 24 classical benchmark functions(including high-dimensional cases),the CEC2017 suite,and the CEC2022 suite.MCPSFOA achieves superior overall performance with Friedman mean ranks of 2.208,2.310 and 2.417 on these benchmark functions,outperforming 11 state-of-the-art algorithms.Furthermore,the practical applicability of MCPSFOA is confirmed through its successful application to five engineering optimization cases,where it also yields excellent results.In conclusion,MCPSFOA is not only a highly effective and reliable optimizer for benchmark functions,but also a practical tool for solving real-world optimization problems.展开更多
Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although th...Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
Childhood neuroblastoma,a leading cause of cancer-related mortality in young children,accounts for approximately 8%-10%of pediatric cancers1.Originating from neural crest cells of the sympathetic nervous system,these ...Childhood neuroblastoma,a leading cause of cancer-related mortality in young children,accounts for approximately 8%-10%of pediatric cancers1.Originating from neural crest cells of the sympathetic nervous system,these tumors affect primarily children younger than 5 years of age and are often diagnosed in advanced stages,because of their aggressive nature and vague early symptoms2-4.展开更多
Neural crest-derived mesenchymal stem cells(NC-MSCs)represent a unique population with remarkable regenerative potential,owing to their embryonic origin and exceptional differentiation capacity.These cells demonstrate...Neural crest-derived mesenchymal stem cells(NC-MSCs)represent a unique population with remarkable regenerative potential,owing to their embryonic origin and exceptional differentiation capacity.These cells demonstrate superior performance in neural and craniofacial tissue regeneration compared to conventional mesenchymal stem cells,with dental stem cells emerging as particularly promising candidates for clinical applications in periodontics and endodontics.Despite their therapeutic promise,adult NC-MSCs face significant challenges including donor site limitations,cellular heterogeneity,and scalability issues.Recent advances in pluripotent stem cell offer potential solutions through the generation of NC-MSCs in vitro,though safety concerns regarding tumorigenicity and long-term stability remain to be addressed through comprehensive preclinical studies.This review provides a comprehensive analysis of NC-MSC biology,highlighting their developmental origins,molecular characteristics,and current applications in regenerative medicine.We critically evaluate existing challenges and future directions,emphasizing the need for standardized protocols,improved characterization methods,and rigorous preclinical evaluation to facilitate clinical translation and therapeutic implementation.展开更多
Autism spectrum disorder(ASD)is a multifaceted neurological developmental condition that manifests in several ways.Nearly all autistic children remain undiagnosed before the age of three.Developmental problems affecti...Autism spectrum disorder(ASD)is a multifaceted neurological developmental condition that manifests in several ways.Nearly all autistic children remain undiagnosed before the age of three.Developmental problems affecting face features are often associated with fundamental brain disorders.The facial evolution of newborns with ASD is quite different from that of typically developing children.Early recognition is very significant to aid families and parents in superstition and denial.Distinguishing facial features from typically developing children is an evident manner to detect children analyzed with ASD.Presently,artificial intelligence(AI)significantly contributes to the emerging computer-aided diagnosis(CAD)of autism and to the evolving interactivemethods that aid in the treatment and reintegration of autistic patients.This study introduces an Ensemble of deep learning models based on the autism spectrum disorder detection in facial images(EDLM-ASDDFI)model.The overarching goal of the EDLM-ASDDFI model is to recognize the difference between facial images of individuals with ASD and normal controls.In the EDLM-ASDDFI method,the primary level of data pre-processing is involved by Gabor filtering(GF).Besides,the EDLM-ASDDFI technique applies the MobileNetV2 model to learn complex features from the pre-processed data.For the ASD detection process,the EDLM-ASDDFI method uses ensemble techniques for classification procedure that encompasses long short-term memory(LSTM),deep belief network(DBN),and hybrid kernel extreme learning machine(HKELM).Finally,the hyperparameter selection of the three deep learning(DL)models can be implemented by the design of the crested porcupine optimizer(CPO)technique.An extensive experiment was conducted to emphasize the improved ASD detection performance of the EDLM-ASDDFI method.The simulation outcomes indicated that the EDLM-ASDDFI technique highlighted betterment over other existing models in terms of numerous performance measures.展开更多
The mandibular condyle is a critical growth center in craniofacial bone development,especially during postnatal stages.Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signa...The mandibular condyle is a critical growth center in craniofacial bone development,especially during postnatal stages.Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks.Plagl1,which encodes a zinc finger transcription factor,is a paternally expressed gene.We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell(CNCC)-derived lineage cells in mouse condyles.Using the CNCC-derived lineage-specific Plagl1 knockout mouse model,we evaluate the function of PLAGL1 during postnatal mouse condyle development.Our findings show that PLAGL1 contributes significantly to osteoblast differentiation,and its deficiency impairs osteogenic lineage differentiation,which consequently disrupts mandibular condyle development.Mechanistically,insulin-like growth factor 2(IGF2)in complex with IGF-binding proteins(IGFBPs)has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis.Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway,leading to disordered glucose metabolism,defective extracellular matrix organization,and impaired ossification.Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency.In conclusion,the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.展开更多
基金supported by the National Natural Science Foundation of China(No.49706067)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry.
文摘A clear definition of 3-D wave crest and a description of the procedures to detect the boundary of wave crest are presented in the paper. By using random wave theory and directional wave spectrum, a MATLAB-platformed program is designed to simulate random wave crests for various directional spectral conditions in deep water. Statistics of wave crests with different directional spreading parameters and different directional functions are obtained and discussed.
基金supported by National Natural Science Foundation of China(No.32370545)Key R&D Program of Zhejiang Province(No.2021C02044)Zhejiang Rare and Endangered Wildlife Rescue and Conservation Project(2021–2025)。
文摘The critically endangered Chinese Crested Tern(CThalasseus bernsteini,CCT)and its common flocking companion,the Greater Crested Tern(Thalasseus bergii,GCT),have been the focus of targeted recovery efforts in the Jiushan Archipelago of Zhejiang Province,China since 2013.To evaluate the long-term effectiveness of these measures and address key knowledge gaps in population dynamics and migration ecology,we analyzed ten years(2015-2024)of banding and citizen science data,comprising 116 CCT and 3501 GCT resighting records.We estimated survival rates using both directly derived survival rate(based on resighting rate after two years)and Cormack-Jolly-Seber modeling,and examined migration connectivity and climate risks.Results showed robust juvenile survival:modeled survival for the tern chick population was lower in the first two years(63.9±12.0%)but exceeded 78%thereafter.This was also supported by resighting rate after two years:CCT 77.27%,GCT70.42%.A key divergence in post-breeding migration was identified:CCT moves northward to stopover sites such as Nantong,Rizhao,and Jiaozhou Bay,whereas GCT migrates southward.Climate data confirmed that northern stopover sites do not pose higher storm risks,indicating that CCT's northward migration is not a population liability.Furthermore,connectivity among breeding islands in Zhejiang and the Matsu Archipelago reveals a nascent coastal breeding network along China's coast.These findings underscore the importance of protecting both the northern migration route and the breeding island network to ensure full life-cycle conservation of CCT.
基金supported by the National Natural Science Foundation of China(Grant No.12402139,No.52368070)supported by Hainan Provincial Natural Science Foundation of China(Grant No.524QN223)+3 种基金Scientific Research Startup Foundation of Hainan University(Grant No.RZ2300002710)State Key Laboratory of Structural Analysis,Optimization and CAE Software for Industrial Equipment,Dalian University of Technology(Grant No.GZ24107)the Horizontal Research Project(Grant No.HD-KYH-2024022)Innovative Research Projects for Postgraduate Students in Hainan Province(Grant No.Hys2025-217).
文摘Optimization problems are prevalent in various fields of science and engineering,with several real-world applications characterized by high dimensionality and complex search landscapes.Starfish optimization algorithm(SFOA)is a recently optimizer inspired by swarm intelligence,which is effective for numerical optimization,but it may encounter premature and local convergence for complex optimization problems.To address these challenges,this paper proposes the multi-strategy enhanced crested porcupine-starfish optimization algorithm(MCPSFOA).The core innovation of MCPSFOA lies in employing a hybrid strategy to improve SFOA,which integrates the exploratory mechanisms of SFOA with the diverse search capacity of the Crested Porcupine Optimizer(CPO).This synergy enhances MCPSFOA’s ability to navigate complex and multimodal search spaces.To further prevent premature convergence,MCPSFOA incorporates Lévy flight,leveraging its characteristic long and short jump patterns to enable large-scale exploration and escape from local optima.Subsequently,Gaussian mutation is applied for precise solution tuning,introducing controlled perturbations that enhance accuracy and mitigate the risk of insufficient exploitation.Notably,the population diversity enhancement mechanism periodically identifies and resets stagnant individuals,thereby consistently revitalizing population variety throughout the optimization process.MCPSFOA is rigorously evaluated on 24 classical benchmark functions(including high-dimensional cases),the CEC2017 suite,and the CEC2022 suite.MCPSFOA achieves superior overall performance with Friedman mean ranks of 2.208,2.310 and 2.417 on these benchmark functions,outperforming 11 state-of-the-art algorithms.Furthermore,the practical applicability of MCPSFOA is confirmed through its successful application to five engineering optimization cases,where it also yields excellent results.In conclusion,MCPSFOA is not only a highly effective and reliable optimizer for benchmark functions,but also a practical tool for solving real-world optimization problems.
基金supported by the National Natural Science Foundation of China(No.82271889,82572117,82371173,82172105)the National Key Research and Development Program of China(No.2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400)。
文摘Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82470544)the Fundamental Research Funds for the Central Universities(Grant No.226-2024-00153).
文摘Childhood neuroblastoma,a leading cause of cancer-related mortality in young children,accounts for approximately 8%-10%of pediatric cancers1.Originating from neural crest cells of the sympathetic nervous system,these tumors affect primarily children younger than 5 years of age and are often diagnosed in advanced stages,because of their aggressive nature and vague early symptoms2-4.
基金Supported by the National Natural Science Foundation of China,No.82270951.
文摘Neural crest-derived mesenchymal stem cells(NC-MSCs)represent a unique population with remarkable regenerative potential,owing to their embryonic origin and exceptional differentiation capacity.These cells demonstrate superior performance in neural and craniofacial tissue regeneration compared to conventional mesenchymal stem cells,with dental stem cells emerging as particularly promising candidates for clinical applications in periodontics and endodontics.Despite their therapeutic promise,adult NC-MSCs face significant challenges including donor site limitations,cellular heterogeneity,and scalability issues.Recent advances in pluripotent stem cell offer potential solutions through the generation of NC-MSCs in vitro,though safety concerns regarding tumorigenicity and long-term stability remain to be addressed through comprehensive preclinical studies.This review provides a comprehensive analysis of NC-MSC biology,highlighting their developmental origins,molecular characteristics,and current applications in regenerative medicine.We critically evaluate existing challenges and future directions,emphasizing the need for standardized protocols,improved characterization methods,and rigorous preclinical evaluation to facilitate clinical translation and therapeutic implementation.
基金Researchers supporting Project number(RSPD2025R1107),King Saud University,Riyadh,Saudi Arabia.
文摘Autism spectrum disorder(ASD)is a multifaceted neurological developmental condition that manifests in several ways.Nearly all autistic children remain undiagnosed before the age of three.Developmental problems affecting face features are often associated with fundamental brain disorders.The facial evolution of newborns with ASD is quite different from that of typically developing children.Early recognition is very significant to aid families and parents in superstition and denial.Distinguishing facial features from typically developing children is an evident manner to detect children analyzed with ASD.Presently,artificial intelligence(AI)significantly contributes to the emerging computer-aided diagnosis(CAD)of autism and to the evolving interactivemethods that aid in the treatment and reintegration of autistic patients.This study introduces an Ensemble of deep learning models based on the autism spectrum disorder detection in facial images(EDLM-ASDDFI)model.The overarching goal of the EDLM-ASDDFI model is to recognize the difference between facial images of individuals with ASD and normal controls.In the EDLM-ASDDFI method,the primary level of data pre-processing is involved by Gabor filtering(GF).Besides,the EDLM-ASDDFI technique applies the MobileNetV2 model to learn complex features from the pre-processed data.For the ASD detection process,the EDLM-ASDDFI method uses ensemble techniques for classification procedure that encompasses long short-term memory(LSTM),deep belief network(DBN),and hybrid kernel extreme learning machine(HKELM).Finally,the hyperparameter selection of the three deep learning(DL)models can be implemented by the design of the crested porcupine optimizer(CPO)technique.An extensive experiment was conducted to emphasize the improved ASD detection performance of the EDLM-ASDDFI method.The simulation outcomes indicated that the EDLM-ASDDFI technique highlighted betterment over other existing models in terms of numerous performance measures.
基金sponsored by funding from the National Natural Science Foundation of China(82201004 to J.D.,81921002 to X.J.,82130027 to X.J.)the Young Elite Scientists Sponsorship Program by CAST(YESS20230102 to J.D.)the innovative research team of high-level local universities in Shanghai(SHSMU-ZLCX20212400 to X.J.).
文摘The mandibular condyle is a critical growth center in craniofacial bone development,especially during postnatal stages.Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks.Plagl1,which encodes a zinc finger transcription factor,is a paternally expressed gene.We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell(CNCC)-derived lineage cells in mouse condyles.Using the CNCC-derived lineage-specific Plagl1 knockout mouse model,we evaluate the function of PLAGL1 during postnatal mouse condyle development.Our findings show that PLAGL1 contributes significantly to osteoblast differentiation,and its deficiency impairs osteogenic lineage differentiation,which consequently disrupts mandibular condyle development.Mechanistically,insulin-like growth factor 2(IGF2)in complex with IGF-binding proteins(IGFBPs)has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis.Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway,leading to disordered glucose metabolism,defective extracellular matrix organization,and impaired ossification.Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency.In conclusion,the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.
