Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic d...Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.展开更多
Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ions.However,there is ...Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ions.However,there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone metabolism.In this study,we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells,which resulted in impaired mitochondrial morphology and function.Consequently,this impairment hindered the bone formation of mesenchymal stem cells,resulting in osteopenia in mice.Mechanically,the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission,which inhibited the classical Wnt signaling pathway.Furthermore,the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem cells.This study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery.展开更多
For A∈CmΧn, if the sum of the elements in each row and the sum of the elements in each column are both equal to 0, then A is called an indeterminate admittance matrix. If A is an indeterminate admit...For A∈CmΧn, if the sum of the elements in each row and the sum of the elements in each column are both equal to 0, then A is called an indeterminate admittance matrix. If A is an indeterminate admittance matrix and a Hermitian matrix, then A is called a Hermitian indeterminate admittance matrix. In this paper, we provide two methods to study the least squares Hermitian indeterminate admittance problem of complex matrix equation (AXB,CXD)=(E,F), and give the explicit expressions of least squares Hermitian indeterminate admittance solution with the least norm in each method. We mainly adopt the Moore-Penrose generalized inverse and Kronecker product in Method I and a matrix-vector product in Method II, respectively.展开更多
Raw Global Positioning System (GPS) data can provide rich context information for behaviour understanding and transport planning. However, they are not yet fully understood, and fine-grained identification of transpor...Raw Global Positioning System (GPS) data can provide rich context information for behaviour understanding and transport planning. However, they are not yet fully understood, and fine-grained identification of transportation mode is required. In this paper, we present a robust framework without geographic information, which can effectively and automatically identify transportation modes including car, bus, bike and walk. Firstly, a trajectory segmentation algorithm is designed to divide raw GPS trajectory into single mode segments. Secondly, several modern features are proposed which are more discriminating than traditional features. At last, an additional postprocessing procedure is adopted with considering the wholeness of trajectory. Based on Random Forest classifier, our framework can achieve a promising accuracy by distance of 82.85% for identifying transportation modes and especially 91.44% for car mode.展开更多
Understanding meaningful information such as transportation mode(e.g.,walking,bus)from Global Positioning System(GPS)data has great advantages in urban management and environmental protection.However,the urban traffic...Understanding meaningful information such as transportation mode(e.g.,walking,bus)from Global Positioning System(GPS)data has great advantages in urban management and environmental protection.However,the urban traffic environment has evolved from“data poor”to“data rich”,resulting in the decline in the accuracy of transportation mode detection results.In this paper,an enhanced approach for effectively detecting transportation mode with a detection model and correction method from GPS data is proposed.Specifically,we make the following contributions.First,a trajectory segmentation method is proposed to detect single-mode segments.Secondly,a Random Forest(RF)-based detection model containing several new features is introduced to enhance discrimination.Finally,a correction method is designed to improve the detection performance,which is based on the mode probability of the current segment and its adjacent segments.The results of our detection model and correction method outperform state-of-the-art research in transportation mode detection.展开更多
基金This work was supported by the Natural Science Foundation of China(Nos.81870747,82170916)Clinical Medicine Plus X–Young Scholars Project(PKU2021LCXQ003)the Fundamental Research Funds for the Central Universities(BMU2021YJ001).
文摘Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2022YFA1105800)the National Natural Science Foundation of China(No.81970940(R.L.Y.))+1 种基金Research Foundation of Peking University School and Hospital of Stomatology(No.PKUSS20230103)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(No.GZC20230136).
文摘Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ions.However,there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone metabolism.In this study,we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells,which resulted in impaired mitochondrial morphology and function.Consequently,this impairment hindered the bone formation of mesenchymal stem cells,resulting in osteopenia in mice.Mechanically,the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission,which inhibited the classical Wnt signaling pathway.Furthermore,the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem cells.This study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery.
文摘For A∈CmΧn, if the sum of the elements in each row and the sum of the elements in each column are both equal to 0, then A is called an indeterminate admittance matrix. If A is an indeterminate admittance matrix and a Hermitian matrix, then A is called a Hermitian indeterminate admittance matrix. In this paper, we provide two methods to study the least squares Hermitian indeterminate admittance problem of complex matrix equation (AXB,CXD)=(E,F), and give the explicit expressions of least squares Hermitian indeterminate admittance solution with the least norm in each method. We mainly adopt the Moore-Penrose generalized inverse and Kronecker product in Method I and a matrix-vector product in Method II, respectively.
文摘Raw Global Positioning System (GPS) data can provide rich context information for behaviour understanding and transport planning. However, they are not yet fully understood, and fine-grained identification of transportation mode is required. In this paper, we present a robust framework without geographic information, which can effectively and automatically identify transportation modes including car, bus, bike and walk. Firstly, a trajectory segmentation algorithm is designed to divide raw GPS trajectory into single mode segments. Secondly, several modern features are proposed which are more discriminating than traditional features. At last, an additional postprocessing procedure is adopted with considering the wholeness of trajectory. Based on Random Forest classifier, our framework can achieve a promising accuracy by distance of 82.85% for identifying transportation modes and especially 91.44% for car mode.
文摘Understanding meaningful information such as transportation mode(e.g.,walking,bus)from Global Positioning System(GPS)data has great advantages in urban management and environmental protection.However,the urban traffic environment has evolved from“data poor”to“data rich”,resulting in the decline in the accuracy of transportation mode detection results.In this paper,an enhanced approach for effectively detecting transportation mode with a detection model and correction method from GPS data is proposed.Specifically,we make the following contributions.First,a trajectory segmentation method is proposed to detect single-mode segments.Secondly,a Random Forest(RF)-based detection model containing several new features is introduced to enhance discrimination.Finally,a correction method is designed to improve the detection performance,which is based on the mode probability of the current segment and its adjacent segments.The results of our detection model and correction method outperform state-of-the-art research in transportation mode detection.
