Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-deriv...Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.展开更多
New Delhi metallo-β-lactamase 1(NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relative...New Delhi metallo-β-lactamase 1(NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relatively weak due to the shallow active pocket of NDM-1. Alternatively, irreversible covalent inhibitors can prevent their dissociation from the target, leading to permanent inactivation of the protein.Herein, we report a series of irreversible covalent inhibitors of NDM-1 targeting the conserved Lys211 in the active pocket. Several methods, including mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorescent labeling, and coumarin probe were used to demonstrate that pentafluorophenyl ester formed a covalent bond with Lys211. Moreover, our target inhibitor, in combination with meropenem, achieved an antibacterial effect on drug-resistant bacteria, along with an excellent safety profile. Our new strategy in designing lysine-targeted irreversible covalent NDM-1 inhibitors provides a potential option for the clinical treatment of Gram-negative bacteria.展开更多
Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems.Nevertheless,the strategy of directly integrating modules cannot easily fulfill the re...Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems.Nevertheless,the strategy of directly integrating modules cannot easily fulfill the requirements of common applications,e.g.,the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests.Here,we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics.Double-layer 3D microfluidic structures can be produced by replicating the assembled molds.A library of modularized molds is presented for flow control,droplet generation and manipulation and cell trapping and coculture.In addition,a variety of modularized attachments,including valves,light sources and microscopic cameras,have been developed with the capability to be mounted onto chips on demand.Microfluidic systems,including those for concentration gradient generation,droplet-based microfluidics,cell trapping and drug screening,are demonstrated.This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms,with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing.展开更多
In this article,we demonstrated a handheld smartphone fluorescence microscope(HSFM)that integrates dualfunctional polymer lenses with a smartphone.The HSFM consists of a smartphone,a field-portable illumination source...In this article,we demonstrated a handheld smartphone fluorescence microscope(HSFM)that integrates dualfunctional polymer lenses with a smartphone.The HSFM consists of a smartphone,a field-portable illumination source,and a dual-functional polymer lens that performs both optical imaging and filtering.Therefore,compared with the existing smartphone fluorescence microscope,the HSFM does not need any additional optical filters.Although fluorescence imaging has traditionally played an indispensable role in biomedical and clinical applications due to its high specificity and sensitivity for detecting cells,proteins,DNAs/RNAs,etc.,the bulky elements of conventional fluorescence microscopes make them inconvenient for use in point-of-care diagnosis.The HSFM demonstrated in this article solves this problem by providing a multifunctional,miniature,small-form-factor fluorescence module.This multifunctional fluorescence module can be seamlessly attached to any smartphone camera for both bright-field and fluorescence imaging at cellular-scale resolutions without the use of additional bulky lenses/filters;in fact,the HSFM achieves magnification and light filtration using a single lens.Cell and tissue observation,cell counting,plasmid transfection evaluation,and superoxide production analysis were performed using this device.Notably,this lens system has the unique capability of functioning with numerous smartphones,irrespective of the smartphone model and the camera technology housed within each device.As such,this HSFM has the potential to pave the way for realtime point-of-care diagnosis and opens up countless possibilities for personalized medicine.展开更多
This study provides a rapid method for quantification of mineral oil in rapeseed oil using near-infrared spectroscopy.The data were processed by direct orthogonal signal correction(DOSC),successive projections algorit...This study provides a rapid method for quantification of mineral oil in rapeseed oil using near-infrared spectroscopy.The data were processed by direct orthogonal signal correction(DOSC),successive projections algorithm(SPA),partial least squares,and principal component regression(PCR).Good correlation coefficients(R)of 0.998 and root-mean-squared error(RMSE)of 0.005 were obtained,and the DOSC-SPA-PCR model was identified as the optimal method.A satisfactory accuracy with R and RMSE of prediction by DOSC-SPA-PCR of 0.990 and 0.006,was obtained.The results demonstrate that the proposed methodology is a promising method for the rapid quantitative detection of mineral oil in vegetable oil.展开更多
基金supported by the National Key Research&Development Program of China(Nos.2021YFC2302400,2021YFA1201000,2021YFE0106900)the National Natural Science Foundation of China(Nos.32171394,32101148,82202338)+2 种基金the Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(No.20220484207)the Beijing Natural Science Foundation(No.L222128)the Fundamental Research Funds for the Central Universities(No.2022CX01013).
文摘Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.
基金funded by the National Natural Science Foundation of China (No. 82073688 to X. Sun and No. 82103971 to Y. Liang)Science and Technology Commission of Shanghai Municipality (No. 21S11907300 to X. Sun)Shanghai Science and Technology Development Fund from Central Leading Local Government (No. YDZX20223100001004 to X. Sun)。
文摘New Delhi metallo-β-lactamase 1(NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relatively weak due to the shallow active pocket of NDM-1. Alternatively, irreversible covalent inhibitors can prevent their dissociation from the target, leading to permanent inactivation of the protein.Herein, we report a series of irreversible covalent inhibitors of NDM-1 targeting the conserved Lys211 in the active pocket. Several methods, including mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorescent labeling, and coumarin probe were used to demonstrate that pentafluorophenyl ester formed a covalent bond with Lys211. Moreover, our target inhibitor, in combination with meropenem, achieved an antibacterial effect on drug-resistant bacteria, along with an excellent safety profile. Our new strategy in designing lysine-targeted irreversible covalent NDM-1 inhibitors provides a potential option for the clinical treatment of Gram-negative bacteria.
基金supported by grants from the National Special Fund for the Development of Major Research Equipment and Instrument(Grant No.2020YFF01014503)National Natural Science Foundation of China(Grant No.61775140)+1 种基金Shanghai Industrial Collaborative Innovation Project(Grant No.2021-cyxt1-kj06)Shanghai Rising-Star Program(Grant No.20QA1407000).
文摘Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems.Nevertheless,the strategy of directly integrating modules cannot easily fulfill the requirements of common applications,e.g.,the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests.Here,we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics.Double-layer 3D microfluidic structures can be produced by replicating the assembled molds.A library of modularized molds is presented for flow control,droplet generation and manipulation and cell trapping and coculture.In addition,a variety of modularized attachments,including valves,light sources and microscopic cameras,have been developed with the capability to be mounted onto chips on demand.Microfluidic systems,including those for concentration gradient generation,droplet-based microfluidics,cell trapping and drug screening,are demonstrated.This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms,with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing.
基金supported by grants from the National Key Research and Development Program of China(Nos.2016YFD0500604,2016YFD0500603)the National Natural Science Foundation of China(Nos.61601292,61775140)Shanghai Science and Technology Commission(No.18142200800).
文摘In this article,we demonstrated a handheld smartphone fluorescence microscope(HSFM)that integrates dualfunctional polymer lenses with a smartphone.The HSFM consists of a smartphone,a field-portable illumination source,and a dual-functional polymer lens that performs both optical imaging and filtering.Therefore,compared with the existing smartphone fluorescence microscope,the HSFM does not need any additional optical filters.Although fluorescence imaging has traditionally played an indispensable role in biomedical and clinical applications due to its high specificity and sensitivity for detecting cells,proteins,DNAs/RNAs,etc.,the bulky elements of conventional fluorescence microscopes make them inconvenient for use in point-of-care diagnosis.The HSFM demonstrated in this article solves this problem by providing a multifunctional,miniature,small-form-factor fluorescence module.This multifunctional fluorescence module can be seamlessly attached to any smartphone camera for both bright-field and fluorescence imaging at cellular-scale resolutions without the use of additional bulky lenses/filters;in fact,the HSFM achieves magnification and light filtration using a single lens.Cell and tissue observation,cell counting,plasmid transfection evaluation,and superoxide production analysis were performed using this device.Notably,this lens system has the unique capability of functioning with numerous smartphones,irrespective of the smartphone model and the camera technology housed within each device.As such,this HSFM has the potential to pave the way for realtime point-of-care diagnosis and opens up countless possibilities for personalized medicine.
基金partially supported by the National Natural Science Foundation of China(NSFC)(No.61775140)。
文摘This study provides a rapid method for quantification of mineral oil in rapeseed oil using near-infrared spectroscopy.The data were processed by direct orthogonal signal correction(DOSC),successive projections algorithm(SPA),partial least squares,and principal component regression(PCR).Good correlation coefficients(R)of 0.998 and root-mean-squared error(RMSE)of 0.005 were obtained,and the DOSC-SPA-PCR model was identified as the optimal method.A satisfactory accuracy with R and RMSE of prediction by DOSC-SPA-PCR of 0.990 and 0.006,was obtained.The results demonstrate that the proposed methodology is a promising method for the rapid quantitative detection of mineral oil in vegetable oil.