Optical-resolution photoacoustic microscopy is a novel imaging technique that combines the advantages of optical and ultrasound imaging,enabling high-resolution visualization of biological tissues at the micrometer sc...Optical-resolution photoacoustic microscopy is a novel imaging technique that combines the advantages of optical and ultrasound imaging,enabling high-resolution visualization of biological tissues at the micrometer scale.However,the divergence of the excited Gaussian beam limits the depth-of-field of the system to less than 100μm,which hinders accurate three-dimensional imaging of living tissues and restrictsits applicability in biological research.Therefore,there is an urgent need for an effective method to enhance the depth-of-field without altering the hardware configuration.This paper presents a photoacoustic microscopy depth-of-field extension method and system based on three-dimensional continuity and sparsity deconvolution.This method utilizes a depth-varying point spread function and incorporates continuity and sparsity con-straints into the deconvolution process to mitigate the effect of background noise,enhancing the stability and accuracy of the depth-of-field extension.Experimental results using tungsten wire phantoms suggest that the depth-of-field of system can be extended to 650 pm,which is 7.2 times greater than conventional system,while improving the resolution of the defocused region by an average factor of 3.5.Furthermore,experiments on zebrafish and nude mouse ears with irregular topologies demonstrate that the proposed method successfully overcomes image blurring and the loss of structural information due to limited depth-of-field.All the results suggest that the system with higher lateral resolution and enhanced depth-of-field has significant potential for a wide range of practical biomedical applications.展开更多
Holographic microscopy has emerged as a vital tool in biomedicine,enabling visualization of microscopic morphological features of tissues and cells in a label-free manner.Recently,deep learning(DL)-based image reconst...Holographic microscopy has emerged as a vital tool in biomedicine,enabling visualization of microscopic morphological features of tissues and cells in a label-free manner.Recently,deep learning(DL)-based image reconstruction models have demonstrated state-of-the-art performance in holographic image reconstruction.However,their utility in practice is still severely limited,as conventional training schemes could not properly handle out-of-distribution data.Here,we leverage backpropagation operation and reparameterization of the forward propagator to enable an adaptable image reconstruction model for histopathologic inspection.Only given with a training dataset of rectum tissue images captured from a single imaging configuration,our scheme consistently shows high reconstruction performance even with the input hologram of diverse tissue types at different pathological states captured under various imaging configurations.Using the proposed adaptation technique,we show that the diagnostic features of cancerous colorectal tissues,such as dirty necrosis,captured with 5×magnification and a numerical aperture(NA)of 0.1,can be reconstructed with high accuracy,whereas a given training dataset is strictly confined to normal rectum tissues acquired under the imaging configuration of 20×magnification and an NA of 0.4.Our results suggest that the DL-based image reconstruction approaches,with sophisticated adaptation techniques,could offer an extensively generalizable solution for inverse mapping problems in imaging.展开更多
The assembly behaviors of two low-symmetric carboxylic acid molecules(50-(6-carboxynaphthalen-2-yl)-[1,10:30,100-triphenyl]-3,400,5-tricarboxylic acid(CTTA)and 30,50-bis(6-carboxynaphthalen-2-yl)-[1,10-biphenyl]-3,5-d...The assembly behaviors of two low-symmetric carboxylic acid molecules(50-(6-carboxynaphthalen-2-yl)-[1,10:30,100-triphenyl]-3,400,5-tricarboxylic acid(CTTA)and 30,50-bis(6-carboxynaphthalen-2-yl)-[1,10-biphenyl]-3,5-dicarboxylic acid(BCBDA))containing naphthalene rings on graphite surfaces have been investigated using scanning tunneling microscopy(STM).The transformation of nanostructures induced by the second components(EDA and PEBP-C4)have been also examined.Both CTTA and BCBDA molecules self-assemble at the 1-heptanoic acid(HA)/HOPG interface,forming porous network structures.The dimer represents the most elementary building unit due to the formation of double hydrogen bonds.Moreover,the flipping of naphthalene ring results in the isomerization of BCBDA molecule.The introduction of carboxylic acid derivative EDA disrupts the dimer,which subsequently undergoes a structural conformation to form a novel porous structure.Furthermore,upon the addition of pyridine derivative PEBP-C4,N–H⋯O hydrogen bonds are the dominant forces driving the three coassembled structures.We have also conducted density functional theory(DFT)calculations to determine the molecular conformation and analyze the mechanisms underlying the formation of nanostructures.展开更多
Two-photon fluorescence microscopy,based on the principles of two-photon excited fluorescence and second harmonic generation,enables real-time non-invasive in vivo imaging of skin and cells,providing a means to assess...Two-photon fluorescence microscopy,based on the principles of two-photon excited fluorescence and second harmonic generation,enables real-time non-invasive in vivo imaging of skin and cells,providing a means to assess human health status.In this paper,a miniaturized two-photon imaging system is designed and fabricated to withstand extreme vibration and shock environments.The mechanical stability of the optical and structural components of the miniaturized probe is evaluated under random vibration and shock vibration tests using finite element simulation methods and ray tracing techniques.During the environmental testing,the maximum stress on the probe is 11.5 MPa,which is well below the threshold for structural failure.The largest structural displacement occurs at the collimator,where random vibrations produce an offset of 10.9μm.This offset is analyzed by using geometric optics and point spread functions.Under the maximum collimator offset,the theoretical resolution,as calculated by the point spread function,shifted from 463.28 nm to 463.48 nm.Additionally,a lateral offset of 127 nm is observed at the center position,which does not significantly impact the imaging performance.Finally,environmental and imaging performance tests are conducted.The system’s measured resolution after the environmental tests is 530 nm,consistent with its resolution prior to testing.Imaging tests are also performed on the skin’s stratum corneum,granular layer,spinous layer,and basal cell layer,revealing clear cellular structural information.These results confirm the device’s potential for applications in extreme shock and vibration environments.展开更多
The ability to control the electrode interfaces in an electrochemical energy storage system is essential for achieving the desired electrochemical performance.However,achieving this ability requires an in-depth unders...The ability to control the electrode interfaces in an electrochemical energy storage system is essential for achieving the desired electrochemical performance.However,achieving this ability requires an in-depth understanding of the detailed interfacial nanostructures of the electrode under electrochemical operating conditions.In-situ transmission electron microscopy(TEM)is one of the most powerful techniques for revealing electrochemical energy storage mechanisms with high spatiotemporal resolution and high sensitivity in complex electrochemical environments.These attributes play a unique role in understanding how ion transport inside electrode nanomaterials and across interfaces under the dynamic conditions within working batteries.This review aims to gain an in-depth insight into the latest developments of in-situ TEM imaging techniques for probing the interfacial nanostructures of electrochemical energy storage systems,including atomic-scale structural imaging,strain field imaging,electron holography,and integrated differential phase contrast imaging.Significant examples will be described to highlight the fundamental understanding of atomic-scale and nanoscale mechanisms from employing state-of-the-art imaging techniques to visualize structural evolution,ionic valence state changes,and strain mapping,ion transport dynamics.The review concludes by providing a perspective discussion of future directions of the development and application of in-situ TEM techniques in the field of electrochemical energy storage systems.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
基金supported by the National Key R&D Program of China[Grant No.2022YFC2402400]the National Natural Science Foundation of China[Grant No.62275062]+2 种基金Project of Shandong Innovation and Startup Community of High-end Medical Apparatus and Instruments[Grant Nos.2023-SGTTXM-002 and 2024-SGTTXM-005]the Shandong Province Technology Innovation Guidance Plan(Central Leading Local Science and Technology Development Fund)[Grant No.YDZX2023115]the Taishan Scholar Special Funding Project of Shandong Province,and the Shandong Laboratory of Advanced Biomaterials and Medical Devices in Weihai[Grant No.ZL202402].
文摘Optical-resolution photoacoustic microscopy is a novel imaging technique that combines the advantages of optical and ultrasound imaging,enabling high-resolution visualization of biological tissues at the micrometer scale.However,the divergence of the excited Gaussian beam limits the depth-of-field of the system to less than 100μm,which hinders accurate three-dimensional imaging of living tissues and restrictsits applicability in biological research.Therefore,there is an urgent need for an effective method to enhance the depth-of-field without altering the hardware configuration.This paper presents a photoacoustic microscopy depth-of-field extension method and system based on three-dimensional continuity and sparsity deconvolution.This method utilizes a depth-varying point spread function and incorporates continuity and sparsity con-straints into the deconvolution process to mitigate the effect of background noise,enhancing the stability and accuracy of the depth-of-field extension.Experimental results using tungsten wire phantoms suggest that the depth-of-field of system can be extended to 650 pm,which is 7.2 times greater than conventional system,while improving the resolution of the defocused region by an average factor of 3.5.Furthermore,experiments on zebrafish and nude mouse ears with irregular topologies demonstrate that the proposed method successfully overcomes image blurring and the loss of structural information due to limited depth-of-field.All the results suggest that the system with higher lateral resolution and enhanced depth-of-field has significant potential for a wide range of practical biomedical applications.
基金supported by the Samsung Research Funding and Incubation Center of Samsung Electronics(Grant No.SRFC-IT2002-03)the Samsung Electronics Co.,Ltd.(Grant No.IO220908-02403-01)+2 种基金the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(Grant Nos.NRF-RS-2021-NR060086 and NRF-RS-2023-00251628)the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government(MSIT)(Grant No RS-2024-00397673)the KAIST-CERAGEM Next Generation Healthcare Research Center.
文摘Holographic microscopy has emerged as a vital tool in biomedicine,enabling visualization of microscopic morphological features of tissues and cells in a label-free manner.Recently,deep learning(DL)-based image reconstruction models have demonstrated state-of-the-art performance in holographic image reconstruction.However,their utility in practice is still severely limited,as conventional training schemes could not properly handle out-of-distribution data.Here,we leverage backpropagation operation and reparameterization of the forward propagator to enable an adaptable image reconstruction model for histopathologic inspection.Only given with a training dataset of rectum tissue images captured from a single imaging configuration,our scheme consistently shows high reconstruction performance even with the input hologram of diverse tissue types at different pathological states captured under various imaging configurations.Using the proposed adaptation technique,we show that the diagnostic features of cancerous colorectal tissues,such as dirty necrosis,captured with 5×magnification and a numerical aperture(NA)of 0.1,can be reconstructed with high accuracy,whereas a given training dataset is strictly confined to normal rectum tissues acquired under the imaging configuration of 20×magnification and an NA of 0.4.Our results suggest that the DL-based image reconstruction approaches,with sophisticated adaptation techniques,could offer an extensively generalizable solution for inverse mapping problems in imaging.
基金financially supported by the National Natural Science Foundation of China(No.22272039)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB36000000)+1 种基金the Youth Program of the Liaoning Education Department(No.LJKQZ20222280)the Jilin Chinese Academy of Sciences-Yanshen Technology Co.,Ltd.
文摘The assembly behaviors of two low-symmetric carboxylic acid molecules(50-(6-carboxynaphthalen-2-yl)-[1,10:30,100-triphenyl]-3,400,5-tricarboxylic acid(CTTA)and 30,50-bis(6-carboxynaphthalen-2-yl)-[1,10-biphenyl]-3,5-dicarboxylic acid(BCBDA))containing naphthalene rings on graphite surfaces have been investigated using scanning tunneling microscopy(STM).The transformation of nanostructures induced by the second components(EDA and PEBP-C4)have been also examined.Both CTTA and BCBDA molecules self-assemble at the 1-heptanoic acid(HA)/HOPG interface,forming porous network structures.The dimer represents the most elementary building unit due to the formation of double hydrogen bonds.Moreover,the flipping of naphthalene ring results in the isomerization of BCBDA molecule.The introduction of carboxylic acid derivative EDA disrupts the dimer,which subsequently undergoes a structural conformation to form a novel porous structure.Furthermore,upon the addition of pyridine derivative PEBP-C4,N–H⋯O hydrogen bonds are the dominant forces driving the three coassembled structures.We have also conducted density functional theory(DFT)calculations to determine the molecular conformation and analyze the mechanisms underlying the formation of nanostructures.
基金supported by the National Natural Science Foundation of China(62475008,62305186).
文摘Two-photon fluorescence microscopy,based on the principles of two-photon excited fluorescence and second harmonic generation,enables real-time non-invasive in vivo imaging of skin and cells,providing a means to assess human health status.In this paper,a miniaturized two-photon imaging system is designed and fabricated to withstand extreme vibration and shock environments.The mechanical stability of the optical and structural components of the miniaturized probe is evaluated under random vibration and shock vibration tests using finite element simulation methods and ray tracing techniques.During the environmental testing,the maximum stress on the probe is 11.5 MPa,which is well below the threshold for structural failure.The largest structural displacement occurs at the collimator,where random vibrations produce an offset of 10.9μm.This offset is analyzed by using geometric optics and point spread functions.Under the maximum collimator offset,the theoretical resolution,as calculated by the point spread function,shifted from 463.28 nm to 463.48 nm.Additionally,a lateral offset of 127 nm is observed at the center position,which does not significantly impact the imaging performance.Finally,environmental and imaging performance tests are conducted.The system’s measured resolution after the environmental tests is 530 nm,consistent with its resolution prior to testing.Imaging tests are also performed on the skin’s stratum corneum,granular layer,spinous layer,and basal cell layer,revealing clear cellular structural information.These results confirm the device’s potential for applications in extreme shock and vibration environments.
基金supported by the National Key Research Program of China under Grant No.2024YFA1408000the National Natural Science Foundation of China(52231007,12327804,T2321003,22088101)+1 种基金in part by the National Key Research Program of China under Grant 2021YFA1200600the support from the U.S.National Science Foundation(CHE 2102482)。
文摘The ability to control the electrode interfaces in an electrochemical energy storage system is essential for achieving the desired electrochemical performance.However,achieving this ability requires an in-depth understanding of the detailed interfacial nanostructures of the electrode under electrochemical operating conditions.In-situ transmission electron microscopy(TEM)is one of the most powerful techniques for revealing electrochemical energy storage mechanisms with high spatiotemporal resolution and high sensitivity in complex electrochemical environments.These attributes play a unique role in understanding how ion transport inside electrode nanomaterials and across interfaces under the dynamic conditions within working batteries.This review aims to gain an in-depth insight into the latest developments of in-situ TEM imaging techniques for probing the interfacial nanostructures of electrochemical energy storage systems,including atomic-scale structural imaging,strain field imaging,electron holography,and integrated differential phase contrast imaging.Significant examples will be described to highlight the fundamental understanding of atomic-scale and nanoscale mechanisms from employing state-of-the-art imaging techniques to visualize structural evolution,ionic valence state changes,and strain mapping,ion transport dynamics.The review concludes by providing a perspective discussion of future directions of the development and application of in-situ TEM techniques in the field of electrochemical energy storage systems.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.