Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We r...Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We retrospectively examined EGFRvⅢ expression and EGFRvⅢ nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization(WHO) II gliomas, 84 WHO Ⅲ gliomas and 72 glioblastomas(WHO IV). Factors that correlated with EGFRvⅢ and EGFRvⅢ nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.Results: Log-rank tests showed that patient age, Karnofsky performance scale(KPS) score, tumor grade,EGFRvⅢ expression, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, isocitrate dehydrogenase(IDH)mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase(MGMT) status(P<0.05) were significantly correlated with overall survival(OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, and IDH mutation(P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvⅢ nuclear translocation(≥7%) had both significantly shorter OS [hazard ratio(HR): 1.920, 95% confidence interval(95% CI): 1.228-3.003, P=0.004] and progression-free survival(PFS) times(HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvⅢ nuclear translocation(<7%).Conclusions: A high level of EGFRvⅢ nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvⅢ expression is not an independent clinical prognostic factor. The level of EGFRvⅢ nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.展开更多
Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine development.However,LNPs also face several challenges,such as toxicity,immun...Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine development.However,LNPs also face several challenges,such as toxicity,immune activation,and low delivery efficiency.To overcome these challenges,artificial intelligence can be used to optimize the design and formulation of LNPs,as well as to predict their properties and performance.Moreover,antibody-targeted conjugation can be used to enhance the specificity and selectivity of LNPs by attaching an antibody that recognizes a specific antigen on the cell surface to LNPs.展开更多
Utilizing biomaterials in tissue engineering has shown considerable promise for tissue regeneration,particularly through delivering multimodel cell-regulatory signals,including the material-related signals and extrins...Utilizing biomaterials in tissue engineering has shown considerable promise for tissue regeneration,particularly through delivering multimodel cell-regulatory signals,including the material-related signals and extrinsic stimuli.In this research,we developed a magnetic-responsive aligned nanofiber fibrin hydrogel(MAFG),integrating the structured alignment of nanofibers and the pliability of fibrin hydrogel with an external magnetic field.This design aimed to enhance the regenerative response in spinal cord injury treatment.A medium-strength magnetic field,aligned with the spinal cord,was applied to aid motor function recovery in rats with spinal cord injuries.The use of MAFG in this context not only intensified the effect of the magnetic field but also encouraged the activation and differentiation of native neural stem cells.Furthermore,this method effectively steered macrophage polarization towards a beneficial M2 phenotype,addressing immune dysregulation at the injury site.The parallel application of magnetic field stimulation through MAFG in a spinal cord injury model contributed to the concurrent promotion of neurogenesis,angiogenesis,and immunomodulation,resulting in marked improvement in motor function in rats.This investigation underscores the therapeutic potential of magnetic field stimulation and highlights how aligning this stimulation with the spinal cord can significantly enhance the regenerative milieu at the injury site.展开更多
3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner.To date,various emergences of living constructs have been bioprinted for in vitro applications,while th...3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner.To date,various emergences of living constructs have been bioprinted for in vitro applications,while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury(SCI)has been relatively overlooked.Herein,living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy.The living nerve-like fibers are comprised of neural stem cells(NSCs)embedded within a designed hydrogel that mimics the extracellular matrix(ECM),assembled into a highly spatial ordered architecture,similar to densely arranged bundles of the nerve fibers.The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model.Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation,angiogenesis,neurogenesis,neural relay formations,and neural circuit remodeling,leading to outstanding functional reconstruction,revealing an evolution process of this living construct after implantation.This effective strategy,based on biomimetic living constructs,opens a new perspective on SCI therapies.展开更多
The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell t...The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell transplantation has become a promising strategy for building a favorable niche to stem cells.Herein,an aligned fibrin nanofiber hydrogel modified with N-Cadherin-Fc(AFGN)was fabricated by electrospinning and biochemical conjugation to deliver NSCs for SCI repair.The AFGN hydrogel provides multimodal cues,including oriented nanofibrous topography,soft stiffness,and specific cell binding ligand,for directing NSC functions and nerve regeneration.The conjugated N-Cadherin-Fc recapitulated the homo-philic cell-cell interaction for NSCs’adhesion on AFGN and modulated cellular mechanosensing in response to AFGN for NSC differentiation.In addition,the AFGN hydrogel carrying exogenous NSCs was implanted in a rat 2 mm-long complete transected SCI model and significantly promoted the grafted NSCs retention,immunomodulation,neuronal differentiation,and in vivo integration with inherent neurons,thus finally achieved renascent neural relay formation and an encouraging locomotor functional recovery.Altogether,this study represents a valuable strategy for boosting NSC-based therapy in SCI regeneration by engineering an NSC-specific niche.展开更多
Flat optics has been considered promising for constructions of spaceborne imaging systems with apertures in excess of 10 m.Despite recent advances,there are long-existing challenges to perform in-phase stitching of mu...Flat optics has been considered promising for constructions of spaceborne imaging systems with apertures in excess of 10 m.Despite recent advances,there are long-existing challenges to perform in-phase stitching of multiple flat optical elements.Phasing the segmented planar instrument has remained at the proof of concept.Here,we achieve autonomous system-level cophasing of a 1.5-m stitching flat device,bridging the gap between the concept and engineering implementation.To do so,we propose a flat element stitching scheme,by manipulating the point spread function,which enables our demonstration of automatically bringing seven flat segments'tip/tilt and piston errors within the tolerance.With phasing done,the 1.5-m system has become the largest phased planar instrument ever built in the world,to our knowledge.The first demonstration of phasing the large practical flat imaging system marks a significant step towards fielding a 10-m class one in space,also paving the way for ultrathin flat imaging in various remote applications.展开更多
基金supported by the National Natural Science Foundation of China (No. 81771309)
文摘Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We retrospectively examined EGFRvⅢ expression and EGFRvⅢ nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization(WHO) II gliomas, 84 WHO Ⅲ gliomas and 72 glioblastomas(WHO IV). Factors that correlated with EGFRvⅢ and EGFRvⅢ nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.Results: Log-rank tests showed that patient age, Karnofsky performance scale(KPS) score, tumor grade,EGFRvⅢ expression, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, isocitrate dehydrogenase(IDH)mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase(MGMT) status(P<0.05) were significantly correlated with overall survival(OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, and IDH mutation(P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvⅢ nuclear translocation(≥7%) had both significantly shorter OS [hazard ratio(HR): 1.920, 95% confidence interval(95% CI): 1.228-3.003, P=0.004] and progression-free survival(PFS) times(HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvⅢ nuclear translocation(<7%).Conclusions: A high level of EGFRvⅢ nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvⅢ expression is not an independent clinical prognostic factor. The level of EGFRvⅢ nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.
文摘Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine development.However,LNPs also face several challenges,such as toxicity,immune activation,and low delivery efficiency.To overcome these challenges,artificial intelligence can be used to optimize the design and formulation of LNPs,as well as to predict their properties and performance.Moreover,antibody-targeted conjugation can be used to enhance the specificity and selectivity of LNPs by attaching an antibody that recognizes a specific antigen on the cell surface to LNPs.
基金funding support from the National Natural Science Foundation of China(No.32271414 and 82201521)the Tsinghua Precision Medicine Foundation(No.2022TS001).
文摘Utilizing biomaterials in tissue engineering has shown considerable promise for tissue regeneration,particularly through delivering multimodel cell-regulatory signals,including the material-related signals and extrinsic stimuli.In this research,we developed a magnetic-responsive aligned nanofiber fibrin hydrogel(MAFG),integrating the structured alignment of nanofibers and the pliability of fibrin hydrogel with an external magnetic field.This design aimed to enhance the regenerative response in spinal cord injury treatment.A medium-strength magnetic field,aligned with the spinal cord,was applied to aid motor function recovery in rats with spinal cord injuries.The use of MAFG in this context not only intensified the effect of the magnetic field but also encouraged the activation and differentiation of native neural stem cells.Furthermore,this method effectively steered macrophage polarization towards a beneficial M2 phenotype,addressing immune dysregulation at the injury site.The parallel application of magnetic field stimulation through MAFG in a spinal cord injury model contributed to the concurrent promotion of neurogenesis,angiogenesis,and immunomodulation,resulting in marked improvement in motor function in rats.This investigation underscores the therapeutic potential of magnetic field stimulation and highlights how aligning this stimulation with the spinal cord can significantly enhance the regenerative milieu at the injury site.
基金The authors thank the financial support from the National Natural Science Foundation of China(Grant No.32271414 and 82201521)the Tsinghua Precision Medicine Foundation(Grant No.2022TS001)the National Key Research and Development Program of China(Grant No.2020YFC1107600).
文摘3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner.To date,various emergences of living constructs have been bioprinted for in vitro applications,while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury(SCI)has been relatively overlooked.Herein,living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy.The living nerve-like fibers are comprised of neural stem cells(NSCs)embedded within a designed hydrogel that mimics the extracellular matrix(ECM),assembled into a highly spatial ordered architecture,similar to densely arranged bundles of the nerve fibers.The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model.Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation,angiogenesis,neurogenesis,neural relay formations,and neural circuit remodeling,leading to outstanding functional reconstruction,revealing an evolution process of this living construct after implantation.This effective strategy,based on biomimetic living constructs,opens a new perspective on SCI therapies.
基金National Natural Science Foundation of China(Grant Nos.32271414 and 82201521)Tsinghua Precision Medicine Foundation(Grant No.2022TS001)National Key Research and Development Program of China(Grant No.2020YFC1107600).
文摘The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell transplantation has become a promising strategy for building a favorable niche to stem cells.Herein,an aligned fibrin nanofiber hydrogel modified with N-Cadherin-Fc(AFGN)was fabricated by electrospinning and biochemical conjugation to deliver NSCs for SCI repair.The AFGN hydrogel provides multimodal cues,including oriented nanofibrous topography,soft stiffness,and specific cell binding ligand,for directing NSC functions and nerve regeneration.The conjugated N-Cadherin-Fc recapitulated the homo-philic cell-cell interaction for NSCs’adhesion on AFGN and modulated cellular mechanosensing in response to AFGN for NSC differentiation.In addition,the AFGN hydrogel carrying exogenous NSCs was implanted in a rat 2 mm-long complete transected SCI model and significantly promoted the grafted NSCs retention,immunomodulation,neuronal differentiation,and in vivo integration with inherent neurons,thus finally achieved renascent neural relay formation and an encouraging locomotor functional recovery.Altogether,this study represents a valuable strategy for boosting NSC-based therapy in SCI regeneration by engineering an NSC-specific niche.
基金National Key Research and Development Program of China (2022YFB3901900)National Natural Science Foundation of China (62005289)+1 种基金Youth Innovation Promotion Association (2020372)Outstanding Scientist Project of Tianfu Qingcheng Program。
文摘Flat optics has been considered promising for constructions of spaceborne imaging systems with apertures in excess of 10 m.Despite recent advances,there are long-existing challenges to perform in-phase stitching of multiple flat optical elements.Phasing the segmented planar instrument has remained at the proof of concept.Here,we achieve autonomous system-level cophasing of a 1.5-m stitching flat device,bridging the gap between the concept and engineering implementation.To do so,we propose a flat element stitching scheme,by manipulating the point spread function,which enables our demonstration of automatically bringing seven flat segments'tip/tilt and piston errors within the tolerance.With phasing done,the 1.5-m system has become the largest phased planar instrument ever built in the world,to our knowledge.The first demonstration of phasing the large practical flat imaging system marks a significant step towards fielding a 10-m class one in space,also paving the way for ultrathin flat imaging in various remote applications.
