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
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various ne...Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.展开更多
Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant i...Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.展开更多
A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy a...A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation.This work reveals immense therapeutic potential for a condition traditionally considered untreatable.However,this milestone achievement also presents new challenges.To translate this pioneering therapy from a single-center success to a global standard,multicenter,controlled clinical trials must be initiated immediately.Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.展开更多
Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplanta...Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.展开更多
BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the commo...BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.展开更多
Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells en...Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.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 Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82471471(to WJ),82471485(to FY)Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation,No.tzjhjw(to WJ)+1 种基金Shaanxi Key Research and Development Plan Project,No.2023-YBSF-353(to XW)the Joint Fund Project of Innovation Research Institute of Xijing Hospital,No.LHJJ24JH13(to ZS)。
文摘Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.
文摘Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.
文摘A recently published prospective study marks a breakthrough for congenital olfactory disorders in children.The study provides the first long-term,three-year follow-up data,robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation.This work reveals immense therapeutic potential for a condition traditionally considered untreatable.However,this milestone achievement also presents new challenges.To translate this pioneering therapy from a single-center success to a global standard,multicenter,controlled clinical trials must be initiated immediately.Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.
基金supported by the National Natural Science Foundation of China,Nos.82271132(to YL),82101167(to BB)the Natural Science Foundation of Chongqing,Nos.CSTB2022NSCQ-MSX0020(to BB),cstc2019jcyj-msxmX0473(to FC).
文摘Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
基金the Ministry of Science and Technology Taiwan,No.MOST 109-2314-B-182A-091,No.NSTC 112-2314-B-182A-062, No.NSTC 113-2314-B-182A-125.
文摘BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.
基金supported by the National Natural Science Foundation of China,No.32171356(to YW)Self-Support Research Projects of Shihezi University,No.ZZZC2021105(to WJ)+1 种基金Capital Medical University Natural Science Cultivation Fund,No.PYZ23044(to FQM)Beijing Municipal Natural Science Foundation,No.7244410(to JHD)。
文摘Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.
