Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detec...Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detection of potentially targetable oncogenic fusions is necessary to select optimal treatment.Detection methods include non-sequencing methods,such as fluorescence in situ hybridization and immunohistochemistry,and sequencing methods,such as DNA-and RNA-based nextgeneration sequencing(NGS).While NGS is an efficient way to analyze multiple genes of interest at once,economic and technical factors may preclude its use in routine care globally,despite several guideline recommendations.The aim of this review is to present a summary of oncogenic gene fusions,with a focus on fusions that affect tyrosine kinase signaling,and to highlight the importance of testing for oncogenic fusions.We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions,and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers.Although treatment options may be limited for patients with rare alterations,healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.展开更多
Dear Editor,Although traditional breeding methods,such as phenotypebased and marker-assisted selection,remain valuable,genomic selection(GS)has emerged as a promising new approach.To address limitations of GS,particul...Dear Editor,Although traditional breeding methods,such as phenotypebased and marker-assisted selection,remain valuable,genomic selection(GS)has emerged as a promising new approach.To address limitations of GS,particularly the time and cost involved in developing training populations,we developed Rice3KGS,a web-based tool that provides access to diverse datasets and integrates analytical functions to support crop breeding efforts.展开更多
Compared with conventional manipulating methods,such as vacuum suction,electromagnetic adsorption,and mechanical clamping,gecko-inspired adhesives possess the ability of attaching on various surfaces with extensive ap...Compared with conventional manipulating methods,such as vacuum suction,electromagnetic adsorption,and mechanical clamping,gecko-inspired adhesives possess the ability of attaching on various surfaces with extensive applications in space operation,industrial manufacturing,etc.However,adhesive structures with high adhesion on one certain surface may lose their adhesive performance when gripping another surface.Achieving a good adhesion on objects with unknown surface morphology in a simple way is still a great challenge for gecko-inspired adhesives.Inspired by the interaction of the gecko’s actuating muscle and adhesive structures,we propose a smart adhesive film to adaptively manipulate objects with unknown surface morphology,consisting of magnetic artificial muscle and mushroom-shaped structures at the microscale.Controlled by the magnetic field,the adhesive film can conformally contact the target surfaces with flat/curved morphology or smooth/rough topography,and easily separated from the contacting interfaces,which process is performed without complex image recognition or detection sensors on predetermining the detailed morphology of the opposing surfaces.This specific characteristic enables the smart adhesive film to successfully grip,transfer and release the unknown objects,extending the operating specification of geckoinspired adhesives.Especially,in the manipulating process,the objects would not be dropped down from the smart adhesive film even if the magnetic field is suddenly removed,which is seldom achieved by other soft grippers.The proposed adhesion strategy extends gecko-inspired adhesives from specific types of surfaces to unknown surface morphology,opening an avenue for the development of gecko-inspired adhesive-based devices and systems.展开更多
Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets...Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin.Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales,from nanometers to micrometers.Single molecule localization microscopy(SMLM)methods,such as STORM,are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.Multi-label imaging of chromatin is necessary to unpack its structural complexity.However,these efforts are challenged by the high-density nuclear environment,which can affect antibody binding affinities,diffusivity and non-specific interactions.Optimizing buffer conditions,fluorophore stability,and antibody specificity is crucial for achieving effective antibody conjugates.Here,we demonstrate a sequential immunolabeling protocol that reliably enables three-color studies within the dense nuclear environment.This protocol couples multiplexed localization datasets with a robust analysis algorithm,which utilizes localizations from one target as seed points for distance,density and multi-label joint affinity measurements to explore complex organization of all three targets.Applying this multiplexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories,but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters.This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy.展开更多
文摘Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detection of potentially targetable oncogenic fusions is necessary to select optimal treatment.Detection methods include non-sequencing methods,such as fluorescence in situ hybridization and immunohistochemistry,and sequencing methods,such as DNA-and RNA-based nextgeneration sequencing(NGS).While NGS is an efficient way to analyze multiple genes of interest at once,economic and technical factors may preclude its use in routine care globally,despite several guideline recommendations.The aim of this review is to present a summary of oncogenic gene fusions,with a focus on fusions that affect tyrosine kinase signaling,and to highlight the importance of testing for oncogenic fusions.We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions,and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers.Although treatment options may be limited for patients with rare alterations,healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.
基金supported by the National Natural Science Foundation of China(32301783 and U21A20214)the Natural Science Foundation of Anhui Province(2308085QC91 and 2408085MC058)+3 种基金the Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-CSIAF202303)the Nanfan special project,CAAS(YYLH2309,YBXM2322,YYLH2401)the Scientific Innovation 2030 Project(2022ZD0401703)the CAAS Innovative Team Award.
文摘Dear Editor,Although traditional breeding methods,such as phenotypebased and marker-assisted selection,remain valuable,genomic selection(GS)has emerged as a promising new approach.To address limitations of GS,particularly the time and cost involved in developing training populations,we developed Rice3KGS,a web-based tool that provides access to diverse datasets and integrates analytical functions to support crop breeding efforts.
基金supported by National Natural Science Foundation(52175546,12102248)the Fundamental Research Funds for the Central Universities of China(grant No.xzd012023046)Funded Project of Shanghai Aerospace Science and Technology(No.SAST2022-078).
文摘Compared with conventional manipulating methods,such as vacuum suction,electromagnetic adsorption,and mechanical clamping,gecko-inspired adhesives possess the ability of attaching on various surfaces with extensive applications in space operation,industrial manufacturing,etc.However,adhesive structures with high adhesion on one certain surface may lose their adhesive performance when gripping another surface.Achieving a good adhesion on objects with unknown surface morphology in a simple way is still a great challenge for gecko-inspired adhesives.Inspired by the interaction of the gecko’s actuating muscle and adhesive structures,we propose a smart adhesive film to adaptively manipulate objects with unknown surface morphology,consisting of magnetic artificial muscle and mushroom-shaped structures at the microscale.Controlled by the magnetic field,the adhesive film can conformally contact the target surfaces with flat/curved morphology or smooth/rough topography,and easily separated from the contacting interfaces,which process is performed without complex image recognition or detection sensors on predetermining the detailed morphology of the opposing surfaces.This specific characteristic enables the smart adhesive film to successfully grip,transfer and release the unknown objects,extending the operating specification of geckoinspired adhesives.Especially,in the manipulating process,the objects would not be dropped down from the smart adhesive film even if the magnetic field is suddenly removed,which is seldom achieved by other soft grippers.The proposed adhesion strategy extends gecko-inspired adhesives from specific types of surfaces to unknown surface morphology,opening an avenue for the development of gecko-inspired adhesive-based devices and systems.
基金supported by NIH grants U54CA268084,U54CA261694,and R01CA228272National Science Foundation grants EFMA-1830961 and CBET-2430743+1 种基金philanthropic support from Rob and Kristin Goldman,Mr.David Sachsthe Christina Carinato Charitable Foundation.
文摘Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin.Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales,from nanometers to micrometers.Single molecule localization microscopy(SMLM)methods,such as STORM,are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.Multi-label imaging of chromatin is necessary to unpack its structural complexity.However,these efforts are challenged by the high-density nuclear environment,which can affect antibody binding affinities,diffusivity and non-specific interactions.Optimizing buffer conditions,fluorophore stability,and antibody specificity is crucial for achieving effective antibody conjugates.Here,we demonstrate a sequential immunolabeling protocol that reliably enables three-color studies within the dense nuclear environment.This protocol couples multiplexed localization datasets with a robust analysis algorithm,which utilizes localizations from one target as seed points for distance,density and multi-label joint affinity measurements to explore complex organization of all three targets.Applying this multiplexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories,but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters.This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy.
