The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patient...The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains un- clear. In this study, 18 healthy subjects and five patients after subacute stroke were included. The five patients were scanned using functional MRI prior to training, 3 weeks after training and at a 12-week follow-up, and then compared with healthy subjects. The FugI-Meyer Assessment and Wolf Motor Function Test scores of the hemiplegic upper limbs of stroke patients were significantly increased 3 weeks after training and at the 12-week follow-up. Functional MRI results showed that contralateral primary sensorimotor cortex was activated after Kinect-based virtual reality training in the stroke patients compared with the healthy subjects. Contralateral primary sensorimotor cortex, the bilateral supplementary motor area and the ipsilateral cerebellum were also activated during hand-clenching in all 18 healthy subjects. Our findings indicate that Kinect-based virtual reality training could promote the recovery of upper limb motor function in subacute stroke patients, and brain reorganization by Kinect-based virtual reality training may be linked to the contralateral sen- sorimotor cortex.展开更多
Photoacoustic microscopy is an in vivo imaging technology based on the photoacoustic effect.It is widely used in various biomedical studies because it can provide high-resolution images while being label-free,safe,and...Photoacoustic microscopy is an in vivo imaging technology based on the photoacoustic effect.It is widely used in various biomedical studies because it can provide high-resolution images while being label-free,safe,and harmless to biological tissue.Polygon-scanning is an effective scanning method in photoacoustic microscopy that can realize fast imaging of biological tissue with a large field of view.However,in polygon-scanning,fluctuations of the rotating motor speed and the geometric error of the rotating mirror cause image distortions,which seriously affect the photoacoustic-microscopy imaging quality.To improve the image quality of photoacoustic microscopy using polygon-scanning,an image correction method is proposed based on accurate ultrasound positioning.In this method,the photoacoustic and ultrasound imaging data of the sample are simultaneously obtained,and the angle information of each mirror used in the polygon-scanning is extracted from the ultrasonic data to correct the photoacoustic images.Experimental results show that the proposed method can significantly reduce image distortions in photoacoustic microscopy,with the image dislocation offset decreasing from 24.774 to 10.365μm.展开更多
Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that...Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that has been approved by Food and Drug Administration(FDA) in USA for the use in indicator-dilution studies in humans. ICG nanoparticles(NPs) have attracted much attention for its potential applications in cancer theranostics. This review focuses on the preparation, application of ICG NPs for in vivo imaging(fluorescent imaging and photoacoustic imaging) and therapeutics(photothermal therapy, photodynamic therapy and photoacoustic therapy), and future directions based on recent developments in these areas. It is hoped that this review might provide new impetus to understand ICG NPs for cancer theranostics.展开更多
Three-dimensional(3D)bioprinting based on traditional 3D printing is an emerging technology that is used to precisely assemble biocompatible materials and cells or bioactive factors into advanced tissue engineering so...Three-dimensional(3D)bioprinting based on traditional 3D printing is an emerging technology that is used to precisely assemble biocompatible materials and cells or bioactive factors into advanced tissue engineering solutions.Similar technology,particularly photo-cured bioprinting strategies,plays an important role in the field of tissue engineering research.The successful implementation of 3D bioprinting is based on the properties of photopolymerized materials.Photocrosslinkable hydrogel is an attractive biomaterial that is polymerized rapidly and enables process control in space and time.Photopolymerization is frequently initiated by ultraviolet(UV)or visible light.However,UV light may cause cell damage and thereby,affect cell viability.Thus,visible light is considered to be more biocompatible than UV light for bioprinting.In this review,we provide an overview of photo curing-based bioprinting technologies,and describe a visible light crosslinkable bioink,including its crosslinking mechanisms,types of visible light initiator,and biomedical applications.We also discuss existing challenges and prospects of visible light-induced 3D bioprinting devices and hydrogels in biomedical areas.展开更多
Digestive tract tumors acount for 15%and 19.3%of the cancer incidence and deaths,respec-tively.Early detection of digestive tract tumors is crucial to the reduction of global cancer burden.Two-photon excitation fuores...Digestive tract tumors acount for 15%and 19.3%of the cancer incidence and deaths,respec-tively.Early detection of digestive tract tumors is crucial to the reduction of global cancer burden.Two-photon excitation fuorescence lifetime imaging microscopy(TP-FLIM)allows non-invasive,label free,three-dimensional,high-resolution imaging of living tisues with not only histological but also biochemical characterization ability in both qualitative and quantitative way.Benefiting from these advantages,this technology is protmising for clinical diagnosis of digestive tract tumors.In recent years,many efforts have'been made in this field and some remarkable progress has been achieved.In this paper,we overview the recent progress of TP-FLIM-based researches on digestive tract tumor detection.Among them,our latest results on the gastric cancer and esophageal cancer are elaborately depicted.Finally,we outlook and discuss the potential advantages and challenges of TP-FLIM in future clinical applications.展开更多
Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo ima...Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo imaging of biological processes in physiology and pathology with high signal-to-noise ratio, but also for clinical diagnosis. In this review, we provide an overview of the recent progress on NIR probes,focusing on fundamental mechanisms of NIR dyes and nanoparticles, and protein engineering strategies for NIR proteins.展开更多
Focused ultrasound(FUS)-induced blood–brain barrier(BBB) opening is crucial for enhancing glioblastoma(GBM) therapies. However, an in vivo imaging approach with a high spatial–temporal resolution to monitor the BBB ...Focused ultrasound(FUS)-induced blood–brain barrier(BBB) opening is crucial for enhancing glioblastoma(GBM) therapies. However, an in vivo imaging approach with a high spatial–temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green(ICG)-dopped microbubbles(MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy(PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window(NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ~168.9 lm and ultrasound penetration depth of ~7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-tobackground ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.展开更多
Targeted therapy of Parkinson’s disease is an important challenge because of the blood–brain barrier limitation.Here,we propose a natural killer cell membrane biomimetic nanocomplex(named BLIPO-CUR)delivered via the...Targeted therapy of Parkinson’s disease is an important challenge because of the blood–brain barrier limitation.Here,we propose a natural killer cell membrane biomimetic nanocomplex(named BLIPO-CUR)delivered via the meningeal lymphatic vessel(MLV)route to further the therapeutic efficacy of Parkinson’s disease.The membrane incorporation enables BLIPO-CUR to target the damaged neurons,thus improving their therapeutic efficacy through clearing reactive oxygen species,suppressing the aggregation ofα-synuclein,and inhibiting the spread of excessα-synuclein species.Compared with the conventional intravenous injection,this MLV administration can enhance the delivered efficiency of curcumin into the brain by~20 folds.The MLV route administration of BLIPO-CUR enhances the treatment efficacy of Parkinson’s disease in mouse models by improving their movement disorders and reversing neuron death.Our findings highlight the great potential of MLV route administration used as targeted delivery of drugs to the brain,holding a great promise for neurodegenerative disease therapy.展开更多
Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research....Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research.However,its layer-by-layer scanning to form a three-dimensional image inherently limits the volumetric imaging speed and increases phototoxicity significantly.In this study,we develop a gradient excitation technique to accelerate TPM volumetric imaging.The axial positions of the fluorophores can be decoded from the intensity ratio of the paired images obtained by sequentially exciting the specimen with two axially elongated two-photon beams of complementary gradient intensities.We achieved a 0.63μm axial localization precision and demonstrate the flexibility of the gradient TPM on various sparsely labeled samples,including bead phantoms,mouse brain tissues,and live macrophages.Compared with traditional TPM,our technique improves volumetric imaging speed(by at least sixfold),decreases photobleaching(i.e.,less than 2.07±2.89%in 25 min),and minimizes photodamages.展开更多
Superparamagnetic iron oxide(SPIO)nanoparticles play an important role in mediating precise and effective magnetic neurostimulation and can help overcome limitations related to penetration depth and spatial resolution...Superparamagnetic iron oxide(SPIO)nanoparticles play an important role in mediating precise and effective magnetic neurostimulation and can help overcome limitations related to penetration depth and spatial resolution.However,nanoparticles readily diffuse in vivo,decreasing the spatial resolution and activation efficiency.In this study,we employed a microfluidic means to fabricate injectable microhydrogels encapsulated with SPIO nanoparticles,which significantly improved the stability of nanoparticles,increased the magnetic properties,reinforced the stimulation effectivity.The fabricated magnetic microhydrogels were highly uniform in size and sphericity,enabling minimally invasive injection into brain tissue.The long-term residency in the cortex up to 22 weeks and the safety of brain tissue were shown using a mouse model.In addition,we quantitatively determined the magneto-mechanical force yielded by only one magnetic microhydrogel using a video-based method.The force was found to be within 7–8 pN under 10 Hz magnetic stimulation by both theoretical simulation and experimental measurement.Lastly,electrophysiological measurement of brain slices showed that the magnetic microhydrogels offer significant advantages in terms of neural activation relative to dissociative SPIO nanoparticles.A universal strategy is thus offered for performing magnetic neuro-stimulation with an improved prospect for biomedical translation.展开更多
Biodegradable polymer scaffolds combined with bioactive components which accelerate osteogenesis and angiogenesis have promise for use in clinical bone defect repair.The preclinical acute toxicity evaluation is an ess...Biodegradable polymer scaffolds combined with bioactive components which accelerate osteogenesis and angiogenesis have promise for use in clinical bone defect repair.The preclinical acute toxicity evaluation is an essential assay of implantable biomaterials to assess the biosafety for accelerating clinical translation.We have successfully developed magnesium(Mg)particles and beta-tricalcium phosphate(β-TCP)for incorporation into poly(lactic-co-glycolic acid)(PLGA)porous composite scaffolds(PTM)using low-temperature rapid prototyping three-dimensional-printing technology.The PTM scaffolds have been fully evaluated and found to exhibit excellent osteogenic capacity for bone defect repair.The preclinical evaluation of acute systemic toxicities is essential and important for development of porous scaffolds to facilitate their clinical translation.In this study,acute systemic toxicity of the PTM scaffolds was evaluated in mice by intraperitoneal injection of the extract solutions of the scaffolds.PTM composite scaffolds with different Mg andβ-TCP content(denoted as PT5M,PT10M,and PT15M)were extracted with different tissue culture media,including normal saline,phosphate-buffered saline,and serum-free minimum essential medium,to create the extract solutions.The evaluation was carried out following the National Standard.The acute toxicity was fully evaluated through the collection of extensive data,including serum/organs ion concentration,fluorescence staining,and in vivo median lethal dose measurement.Mg in major organs(heart,liver,and lung),and Mg ion concentrations in serum of mice,after intraperitoneal injection of the extract solutions,were measured and showed that the extract solutions of PT15M caused significant elevation of serum Mg ion concentrations,which exceeded the safety threshold and led to the death of the mice.In contrast,the extract solutions of PT5M and PT10M scaffolds did not cause the death of the injected mice.The median lethal dose of Mg ions in vivo for mice was determined for the first time in this study to be 110.66 mg/kg,and the safety level of serum magnesium toxicity in mice is 5.4 mM,while the calcium serum safety level is determined as 3.4 mM.The study was approved by the Animal Care and Use Committee of Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences(approval No.SIAT-IRB-170401-YGS-LYX-A0346)on April 5,2017.All these results showed that the Mg ion concentration of intraperitoneally-injected extract solutions was a determinant of mouse survival,and a high Mg ion concentration(more than 240 mM)was the pivotal factor contributing to the death of the mice,while changes in pH value showed a negligible effect.The comprehensive acute systemic toxicity evaluation for PTM porous composite scaffolds in this study provided a reference to guide the design and optimization of this composite scaffold and the results demonstrated the preclinical safety of the as-fabricated PTM scaffold with appropriate Mg content,strongly supporting the official registration process of the PTM scaffold as a medical device for clinical translation.展开更多
Carbon dots that exhibit near-infrared fluorescence(NIR CDs)are considered emerging nanomaterials for advanced biomedical applications with low toxicity and superior photostability and targeting compared to currently ...Carbon dots that exhibit near-infrared fluorescence(NIR CDs)are considered emerging nanomaterials for advanced biomedical applications with low toxicity and superior photostability and targeting compared to currently used photoluminescence agents.Despite progress in the synthesis of NIR CDs,there remains a key obstacle to using them as an in vivo theranostic agent.This work demonstrates that the newly developed sulfur and nitrogen codoped NIR CDs are highly efficient in photothermal therapy(PTT)in mouse models(conversion efficiency of 59%)and can be readily visualized by photoluminescence and photoacoustic imaging.The real theranostic potential of NIR CDs is enhanced by their unique biodistribution and targeting.Contrary to all other nanomaterials that have been tested in biomedicine,they are excreted through the body’s renal filtration system.Moreover,after intravenous injection,NIR CDs are accumulated in tumor tissue via passive targeting,without any active species such as antibodies.Due to their accumulation in tumor tissue without the need for intratumor injection,high photothermal conversion,excellent optical and photoacoustic imaging performance,and renal excretion,the developed CDs are suitable for transfer to clinical biomedical practice.展开更多
Patients with bone defects suffer from a high rate of disability and deformity.Poor contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair ef...Patients with bone defects suffer from a high rate of disability and deformity.Poor contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair efficacy.Although self-expanding scaffolds were developed to enhance bone integration,the limitations on the high transition temperature and the unsatisfied bioactivity hindered greatly their clinical application.Herein,we report a near-infrared-responsive and tight-contacting scaffold that comprises of shape memory polyurethane(SMPU)as the thermal-responsive matrix and magnesium(Mg)as the photothermal and bioactive component,which fabricated by the low temperature rapid prototyping(LT-RP)3D printing technology.As designed,due to synergistic effects of the components and the fabrication approach,the composite scaffold possesses a homogeneously porous structure,significantly improved mechanical properties and stable photothermal effects.The programmed scaffold can be heated to recover under near infrared irradiation in 60s.With 4 wt%Mg,the scaffold has the balanced shape fixity ratio of 93.6%and shape recovery ratio of 95.4%.The compressed composite scaffold could lift a 100 g weight under NIR light,which was more than 1700 times of its own weight.The results of the push-out tests and the finite element analysis(FEA)confirmed the tight-contacting ability of the SMPU/4 wt%Mg scaffold,which had a signficant enhancement compared to the scaffold without shape memory effects.Furthermore,The osteopromotive function of the scaffold has been demonstrated through a series of in vitro and in vivo studies.We envision this scaffold can be a clinically effective strategy for robust bone regeneration.展开更多
When light propagates through the edge or middle part of a microparticle’s incoming interface,there is a basic rule that light converges and diverges rapidly or slowly at the output port. These two parts are referred...When light propagates through the edge or middle part of a microparticle’s incoming interface,there is a basic rule that light converges and diverges rapidly or slowly at the output port. These two parts are referred to as the region of rapid change (RRC) and region of slow change (RSC),respectively. Finding the boundary point between RRC and RSC is the key to reveal and expound upon this rule scientifically. Based on the correlation between light convergence–divergence and the slope of emergent light,combined with the relationship between a natural logarithm and growth in physical reality and the second derivative of a function in practical significance,we determine the boundary point between RRC and RSC,namely,the inflection point. From such a perspective,a photonic nanojet (PNJ) and near-field focusing by light irradiation on RSC and RRC,as well as the position of the inflection point under different refractive index contrasts and the field distribution of light focusing,are studied with finite-element-method-based numerical simulation and ray-optics-based theoretical analysis. By illuminating light of different field intensity ratios to the regions divided by the inflection point,we demonstrate the generation of a photonic hook (PH) and the modulation of PNJ/PH in a new manner.展开更多
Fluorescence probes with aggregation-induced emission(AIE)characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution.However,the lack of toxicity studies and deep tissu...Fluorescence probes with aggregation-induced emission(AIE)characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution.However,the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation.Here,we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green(ICG)during a study period of 36 days to demonstrate AIE probes are nontoxic.Furthermore,through bright and nontoxic AIE probes and fluorescence imaging in the second window(NIR-II,1,000-1,700 nm),we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates,breaking the current limitation of millimeter-deep NIR-II fluorescence imaging.Our important findings,i.e.,nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates,may facilitate successful translation of AIE probes in clinical trials.展开更多
Artificial neural networks have shown great proficiency in transforming low-resolution microscopic images into high-resolution images.However,training data remains a challenge,as large-scale open-source databases of m...Artificial neural networks have shown great proficiency in transforming low-resolution microscopic images into high-resolution images.However,training data remains a challenge,as large-scale open-source databases of microscopic images are rare,particularly 3D data.Moreover,the long training times and the need for expensive computational resources have become a burden to the research community.We introduced a deep-learning-based self-supervised volumetric imaging approach,which we termed“Self-Vision.”The self-supervised approach requires no training data,apart from the input image itself.The lightweight network takes just minutes to train and has demonstrated resolution-enhancing power on par with or better than that of a number of recent microscopybased models.Moreover,the high throughput power of the network enables large image inference with less postprocessing,facilitating a large field-of-view(2.45 mm×2.45 mm)using a home-built two-photon microscopy system.Self-Vision can recover images from fourfold undersampled inputs in the lateral and axial dimensions,dramatically reducing the acquisition time.Self-Vision facilitates the use of a deep neural network for 3D microscopy imaging,easing the demanding process of image acquisition and network training for current resolutionenhancing networks.展开更多
Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with s...Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with superior sensitivity and biological selectivity for fluorescence imaging is thus impera-tive.To move forward in this direction,we developed an easy self-assembly method for fabricating apta-mer-anchored rubrene-loaded organic fluorescent nanoprobes.The aptamer-modified organic nanop-robes integrated the best features of the organic light-emitting materials and the aptamers,thus endowing them with excellent cell-targeting capabil-ity,high stability,and good biocompatibility.By using this general method,a variety of biocompatible and highly bright organic fluorescent nanoprobes based on novel organic light-emitting materials with specific recognition could be easily constructed for real-time biosensing and long-term biomedical imaging.展开更多
基金supported by the National Natural Science Foundationof China,No.30973165
文摘The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains un- clear. In this study, 18 healthy subjects and five patients after subacute stroke were included. The five patients were scanned using functional MRI prior to training, 3 weeks after training and at a 12-week follow-up, and then compared with healthy subjects. The FugI-Meyer Assessment and Wolf Motor Function Test scores of the hemiplegic upper limbs of stroke patients were significantly increased 3 weeks after training and at the 12-week follow-up. Functional MRI results showed that contralateral primary sensorimotor cortex was activated after Kinect-based virtual reality training in the stroke patients compared with the healthy subjects. Contralateral primary sensorimotor cortex, the bilateral supplementary motor area and the ipsilateral cerebellum were also activated during hand-clenching in all 18 healthy subjects. Our findings indicate that Kinect-based virtual reality training could promote the recovery of upper limb motor function in subacute stroke patients, and brain reorganization by Kinect-based virtual reality training may be linked to the contralateral sen- sorimotor cortex.
基金This work was supported by the National Natural Science Foundation of ChinaNos.91739117 and 81927807+3 种基金Shenzhen Science and Technology Innovation,No.JCYJ20170413153129570Chinese Academy of Sciences Nos.YJKYYQ20190078 and GJJSTD20180002Shenzhen Key Laboratory for Molecular Imaging,No.ZDSY20130401165820357Guangdong Provincial Key Laboratory of Biomedical Optical Imaging,No.2020B121201010.
文摘Photoacoustic microscopy is an in vivo imaging technology based on the photoacoustic effect.It is widely used in various biomedical studies because it can provide high-resolution images while being label-free,safe,and harmless to biological tissue.Polygon-scanning is an effective scanning method in photoacoustic microscopy that can realize fast imaging of biological tissue with a large field of view.However,in polygon-scanning,fluctuations of the rotating motor speed and the geometric error of the rotating mirror cause image distortions,which seriously affect the photoacoustic-microscopy imaging quality.To improve the image quality of photoacoustic microscopy using polygon-scanning,an image correction method is proposed based on accurate ultrasound positioning.In this method,the photoacoustic and ultrasound imaging data of the sample are simultaneously obtained,and the angle information of each mirror used in the polygon-scanning is extracted from the ultrasonic data to correct the photoacoustic images.Experimental results show that the proposed method can significantly reduce image distortions in photoacoustic microscopy,with the image dislocation offset decreasing from 24.774 to 10.365μm.
基金support for this research from the National Natural Science Foundation of China (Grant No. 81071249, 81171446 and 20905050)Guangdong Innovation Team of Low-cost Healthcare, Science and Technology Key Project of Guangdong (2009A030301010) and Shenzhen (CXB201005250029A, JC201005270326A, JC201005260247A, JC201104220242A)
文摘Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that has been approved by Food and Drug Administration(FDA) in USA for the use in indicator-dilution studies in humans. ICG nanoparticles(NPs) have attracted much attention for its potential applications in cancer theranostics. This review focuses on the preparation, application of ICG NPs for in vivo imaging(fluorescent imaging and photoacoustic imaging) and therapeutics(photothermal therapy, photodynamic therapy and photoacoustic therapy), and future directions based on recent developments in these areas. It is hoped that this review might provide new impetus to understand ICG NPs for cancer theranostics.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2019B010941001)the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(201908141541)Shenzhen Fundamental Research Foundation(GJHZ20170314154845576 and GJHS20170314161106706).
文摘Three-dimensional(3D)bioprinting based on traditional 3D printing is an emerging technology that is used to precisely assemble biocompatible materials and cells or bioactive factors into advanced tissue engineering solutions.Similar technology,particularly photo-cured bioprinting strategies,plays an important role in the field of tissue engineering research.The successful implementation of 3D bioprinting is based on the properties of photopolymerized materials.Photocrosslinkable hydrogel is an attractive biomaterial that is polymerized rapidly and enables process control in space and time.Photopolymerization is frequently initiated by ultraviolet(UV)or visible light.However,UV light may cause cell damage and thereby,affect cell viability.Thus,visible light is considered to be more biocompatible than UV light for bioprinting.In this review,we provide an overview of photo curing-based bioprinting technologies,and describe a visible light crosslinkable bioink,including its crosslinking mechanisms,types of visible light initiator,and biomedical applications.We also discuss existing challenges and prospects of visible light-induced 3D bioprinting devices and hydrogels in biomedical areas.
基金supports from the National Key Research and Development Program of China(2017YFC0110200)Program 973(2015CB755502)+4 种基金the National Natural Science Foundation of China(NSFC)(81571724,81701744,81822023)the Natural Science Foundation of Guangdong Province(2014A030312006,2017A 030310308)the Scientific Instrument Innovation Team of Chinese Academy of Sciences(GJJSTD 20180002)the Shenzhen Science and Technology Program(JCYJ20170818164343304,JCYJ20170818155006471,JCYJ20160608214524052,JCYJ20180507182432303)the SIAT Innovation Program for Excellent Young Researchers(201821).
文摘Digestive tract tumors acount for 15%and 19.3%of the cancer incidence and deaths,respec-tively.Early detection of digestive tract tumors is crucial to the reduction of global cancer burden.Two-photon excitation fuorescence lifetime imaging microscopy(TP-FLIM)allows non-invasive,label free,three-dimensional,high-resolution imaging of living tisues with not only histological but also biochemical characterization ability in both qualitative and quantitative way.Benefiting from these advantages,this technology is protmising for clinical diagnosis of digestive tract tumors.In recent years,many efforts have'been made in this field and some remarkable progress has been achieved.In this paper,we overview the recent progress of TP-FLIM-based researches on digestive tract tumor detection.Among them,our latest results on the gastric cancer and esophageal cancer are elaborately depicted.Finally,we outlook and discuss the potential advantages and challenges of TP-FLIM in future clinical applications.
基金financially supported by the National Key Research and Development Program of China (No. 2017YFA0700403)National Natural Science Foundation of China (Nos. 31670872, 21874145, 2018M633180, 21905296)+1 种基金Shenzhen Science and Technology Innovation Committee (Nos. KQJSCX20170331161420421, JCYJ20170818163925063, JCYJ20170818164040422, GJHS2017031 4160302802)Chinese Academy of Sciences (No. GJJSTD20180002)
文摘Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo imaging of biological processes in physiology and pathology with high signal-to-noise ratio, but also for clinical diagnosis. In this review, we provide an overview of the recent progress on NIR probes,focusing on fundamental mechanisms of NIR dyes and nanoparticles, and protein engineering strategies for NIR proteins.
基金supported by the National Natural Science Foundation of China (92159304, 82171958, 81901812, 81971638, 91859117, 82027803, and 81927807)CAS Key Laboratory of Health Informatics (2011DP173015)+4 种基金the Science and Technology Key Project of Shenzhen(JCYJ20190812163614809, JCYJ20200109114612308, JCYJ2021032 4120011030, JCYJ20190809105207439, JCYJ20220531091408019, and JCYJ20200109114825064)Guangdong Basic and Applied Basic Research Fund (2020A1515110011, 2020A1515010395, and 2022A1515010384)Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province (2020B1212060051)the Key Technology and Equipment R&D Program of Major Science and Technology Infrastructure of Shenzhen (202100102, 202100104)Discipline Construction Project of Guangdong Medical University (4SG21017G)
文摘Focused ultrasound(FUS)-induced blood–brain barrier(BBB) opening is crucial for enhancing glioblastoma(GBM) therapies. However, an in vivo imaging approach with a high spatial–temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green(ICG)-dopped microbubbles(MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy(PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window(NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ~168.9 lm and ultrasound penetration depth of ~7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-tobackground ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.
基金the Natural Science Foundation of China(82171958,81771906,91859117,81901812,82027803,81927807,and 92159304)CAS Key Laboratory of Health Informatics(2011DP173015)+4 种基金the Science and Technology Key Project of Shenzhen(JCYJ20190812163614809,CYJ20200109114612308,andJCYJ20210324120011030)Shenzhen Key Laboratory of Ultrasound Imaging and Therapy(ZDSYS201802061806314)Guangdong Basic and Applied Basic Research Fund(2020A1515110011)the University of Macao(MYRG2022-00054-FHS)Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province(2020B1212060051).
文摘Targeted therapy of Parkinson’s disease is an important challenge because of the blood–brain barrier limitation.Here,we propose a natural killer cell membrane biomimetic nanocomplex(named BLIPO-CUR)delivered via the meningeal lymphatic vessel(MLV)route to further the therapeutic efficacy of Parkinson’s disease.The membrane incorporation enables BLIPO-CUR to target the damaged neurons,thus improving their therapeutic efficacy through clearing reactive oxygen species,suppressing the aggregation ofα-synuclein,and inhibiting the spread of excessα-synuclein species.Compared with the conventional intravenous injection,this MLV administration can enhance the delivered efficiency of curcumin into the brain by~20 folds.The MLV route administration of BLIPO-CUR enhances the treatment efficacy of Parkinson’s disease in mouse models by improving their movement disorders and reversing neuron death.Our findings highlight the great potential of MLV route administration used as targeted delivery of drugs to the brain,holding a great promise for neurodegenerative disease therapy.
基金National Key Research and Development Program of China(2017YFC0110200)National Natural Science Foundation of China(81822023,81927803,91959121,92159104,82071972)+2 种基金Natural Science Foundation of Guangdong Province(2019A1515011746,2020B121201010)Scientific Instrument Innovation Team of Chinese Academy of Sciences(GJJSTD20180002)Shenzhen Basic Research Program(QCYJ20180507182432303,RCJC20200714114433058,ZDSY20130401165820357).
文摘Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research.However,its layer-by-layer scanning to form a three-dimensional image inherently limits the volumetric imaging speed and increases phototoxicity significantly.In this study,we develop a gradient excitation technique to accelerate TPM volumetric imaging.The axial positions of the fluorophores can be decoded from the intensity ratio of the paired images obtained by sequentially exciting the specimen with two axially elongated two-photon beams of complementary gradient intensities.We achieved a 0.63μm axial localization precision and demonstrate the flexibility of the gradient TPM on various sparsely labeled samples,including bead phantoms,mouse brain tissues,and live macrophages.Compared with traditional TPM,our technique improves volumetric imaging speed(by at least sixfold),decreases photobleaching(i.e.,less than 2.07±2.89%in 25 min),and minimizes photodamages.
基金the National Key Research and Development Program of China(No.2021YFA1201403 to J.F.S.)China Science and Technology Innovation 2030-Major Project(Nos.2022ZD0211701 to Z.J.Z.and 2022ZD0211704 to J.F.S.)+2 种基金the National Natural Science Key Foundation of China(Nos.81830040 and 82130042 to Z.J.Z.)the Science and Technology Program of Guangdong(No.2018B030334001 to Z.J.Z.)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX21_0146 to L.X.).
文摘Superparamagnetic iron oxide(SPIO)nanoparticles play an important role in mediating precise and effective magnetic neurostimulation and can help overcome limitations related to penetration depth and spatial resolution.However,nanoparticles readily diffuse in vivo,decreasing the spatial resolution and activation efficiency.In this study,we employed a microfluidic means to fabricate injectable microhydrogels encapsulated with SPIO nanoparticles,which significantly improved the stability of nanoparticles,increased the magnetic properties,reinforced the stimulation effectivity.The fabricated magnetic microhydrogels were highly uniform in size and sphericity,enabling minimally invasive injection into brain tissue.The long-term residency in the cortex up to 22 weeks and the safety of brain tissue were shown using a mouse model.In addition,we quantitatively determined the magneto-mechanical force yielded by only one magnetic microhydrogel using a video-based method.The force was found to be within 7–8 pN under 10 Hz magnetic stimulation by both theoretical simulation and experimental measurement.Lastly,electrophysiological measurement of brain slices showed that the magnetic microhydrogels offer significant advantages in terms of neural activation relative to dissociative SPIO nanoparticles.A universal strategy is thus offered for performing magnetic neuro-stimulation with an improved prospect for biomedical translation.
基金supported by the National Natural Science Foundation of China(Nos.82022045&22007098)Chinese Academy of Sciences(CAS)Interdisciplinary Innovation Team(No.JCTD-2020-19)+4 种基金Shenzhen Double Chain Project for Innovation and Development Industry supported by Bureau of Industry and Information Technology of Shenzhen of China(No.201806081503414910)Shenzhen Fundamental Research Foundation of China(No.JCYJ20190807154807663)Key Laboratory of Health Informatics,Chinese Academy of Sciences,Chinese Academic of Sciences-Hong Kong(CAS-HK)Joint Lab of Biomaterials and Natural Science Foundation of Guangdong Province of China(No.2018A030310670)Shenzhen Engineering Research Centre for Medical Bioactive Materials of China(No.XMHT20190106001)Shenzhen Institute of Advanced Technology(SIAT)Innovation Program for Excellent Young Researchers of China(No.2020001345).
文摘Biodegradable polymer scaffolds combined with bioactive components which accelerate osteogenesis and angiogenesis have promise for use in clinical bone defect repair.The preclinical acute toxicity evaluation is an essential assay of implantable biomaterials to assess the biosafety for accelerating clinical translation.We have successfully developed magnesium(Mg)particles and beta-tricalcium phosphate(β-TCP)for incorporation into poly(lactic-co-glycolic acid)(PLGA)porous composite scaffolds(PTM)using low-temperature rapid prototyping three-dimensional-printing technology.The PTM scaffolds have been fully evaluated and found to exhibit excellent osteogenic capacity for bone defect repair.The preclinical evaluation of acute systemic toxicities is essential and important for development of porous scaffolds to facilitate their clinical translation.In this study,acute systemic toxicity of the PTM scaffolds was evaluated in mice by intraperitoneal injection of the extract solutions of the scaffolds.PTM composite scaffolds with different Mg andβ-TCP content(denoted as PT5M,PT10M,and PT15M)were extracted with different tissue culture media,including normal saline,phosphate-buffered saline,and serum-free minimum essential medium,to create the extract solutions.The evaluation was carried out following the National Standard.The acute toxicity was fully evaluated through the collection of extensive data,including serum/organs ion concentration,fluorescence staining,and in vivo median lethal dose measurement.Mg in major organs(heart,liver,and lung),and Mg ion concentrations in serum of mice,after intraperitoneal injection of the extract solutions,were measured and showed that the extract solutions of PT15M caused significant elevation of serum Mg ion concentrations,which exceeded the safety threshold and led to the death of the mice.In contrast,the extract solutions of PT5M and PT10M scaffolds did not cause the death of the injected mice.The median lethal dose of Mg ions in vivo for mice was determined for the first time in this study to be 110.66 mg/kg,and the safety level of serum magnesium toxicity in mice is 5.4 mM,while the calcium serum safety level is determined as 3.4 mM.The study was approved by the Animal Care and Use Committee of Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences(approval No.SIAT-IRB-170401-YGS-LYX-A0346)on April 5,2017.All these results showed that the Mg ion concentration of intraperitoneally-injected extract solutions was a determinant of mouse survival,and a high Mg ion concentration(more than 240 mM)was the pivotal factor contributing to the death of the mice,while changes in pH value showed a negligible effect.The comprehensive acute systemic toxicity evaluation for PTM porous composite scaffolds in this study provided a reference to guide the design and optimization of this composite scaffold and the results demonstrated the preclinical safety of the as-fabricated PTM scaffold with appropriate Mg content,strongly supporting the official registration process of the PTM scaffold as a medical device for clinical translation.
基金supported by the National Natural Science Foundation of China(Project nos.51602304,91739117,81527024,61335001,and 81771930)the Youth Innovation Promotion Association of CAS+2 种基金the Jilin Province Science and Technology Research(Project nos.20170101191JC,20170101042JC,20160520008JH,and 20150519003JH)the Shenzhen Science and Technology Innovation Commission(Grant no.JCYJ20170307110157501)the support by the Operational Proqramme Research,Development and Education-European Reqional Development Fund,Project No.CZ.02.1.01/0.0/0.0/16-019/0000754 of the Ministry of Education,Youth and Sports of the Czech Republic and the assistance provided by the Research Infrastructure NanoEnviCz supported by the Ministry of Education,Youth and Sports of the Czech Republic under Project L01305 of the Ministry of Education,Youth and Sports of the Czech Republic.
文摘Carbon dots that exhibit near-infrared fluorescence(NIR CDs)are considered emerging nanomaterials for advanced biomedical applications with low toxicity and superior photostability and targeting compared to currently used photoluminescence agents.Despite progress in the synthesis of NIR CDs,there remains a key obstacle to using them as an in vivo theranostic agent.This work demonstrates that the newly developed sulfur and nitrogen codoped NIR CDs are highly efficient in photothermal therapy(PTT)in mouse models(conversion efficiency of 59%)and can be readily visualized by photoluminescence and photoacoustic imaging.The real theranostic potential of NIR CDs is enhanced by their unique biodistribution and targeting.Contrary to all other nanomaterials that have been tested in biomedicine,they are excreted through the body’s renal filtration system.Moreover,after intravenous injection,NIR CDs are accumulated in tumor tissue via passive targeting,without any active species such as antibodies.Due to their accumulation in tumor tissue without the need for intratumor injection,high photothermal conversion,excellent optical and photoacoustic imaging performance,and renal excretion,the developed CDs are suitable for transfer to clinical biomedical practice.
基金supported by National Key R&D Program of China(2021YFE0202600)National Natural Science Foundation of China(82022045,81871767 and 22007098)+7 种基金CAS Interdisciplinary Innovation Team(JCTD-2020-19)Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(201908141541)Key Filed R&D Program of Guangdong Province(2019B010941001)Key Laboratory of Health Informatics,Chinese Academy of Sciences,Shenzhen Fundamental Research Foundation(JCYJ20190807154807663,JCYJ20170818160707101)CAS-HK Joint Lab of Biomaterials,Natural Science Foundation of Guangdong Province(2018A030310670)Natural Science Foundation of Guangdong Province(2018A030310670)Shenzhen Engineering Research Center for Medical Bioactive Materials(XMHT20190106001),China Postdoctoral Science Foundation(2020TQ0338)Special Research Assistant Project of CAS.
文摘Patients with bone defects suffer from a high rate of disability and deformity.Poor contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair efficacy.Although self-expanding scaffolds were developed to enhance bone integration,the limitations on the high transition temperature and the unsatisfied bioactivity hindered greatly their clinical application.Herein,we report a near-infrared-responsive and tight-contacting scaffold that comprises of shape memory polyurethane(SMPU)as the thermal-responsive matrix and magnesium(Mg)as the photothermal and bioactive component,which fabricated by the low temperature rapid prototyping(LT-RP)3D printing technology.As designed,due to synergistic effects of the components and the fabrication approach,the composite scaffold possesses a homogeneously porous structure,significantly improved mechanical properties and stable photothermal effects.The programmed scaffold can be heated to recover under near infrared irradiation in 60s.With 4 wt%Mg,the scaffold has the balanced shape fixity ratio of 93.6%and shape recovery ratio of 95.4%.The compressed composite scaffold could lift a 100 g weight under NIR light,which was more than 1700 times of its own weight.The results of the push-out tests and the finite element analysis(FEA)confirmed the tight-contacting ability of the SMPU/4 wt%Mg scaffold,which had a signficant enhancement compared to the scaffold without shape memory effects.Furthermore,The osteopromotive function of the scaffold has been demonstrated through a series of in vitro and in vivo studies.We envision this scaffold can be a clinically effective strategy for robust bone regeneration.
基金Guangdong Basic and Applied Basic Research Foundation (2019A1515011242)Key-Area Research and Development Program of Guangdong Province(2019B020226004)+2 种基金National Natural Science Foundation of China (61805271,62074155)Shenzhen Science and Technology Innovation Commission(JCYJ20170818154035069,KCXFZ202002011008124)CAS Key Laboratory of Health Informatics (2011DP173015)。
文摘When light propagates through the edge or middle part of a microparticle’s incoming interface,there is a basic rule that light converges and diverges rapidly or slowly at the output port. These two parts are referred to as the region of rapid change (RRC) and region of slow change (RSC),respectively. Finding the boundary point between RRC and RSC is the key to reveal and expound upon this rule scientifically. Based on the correlation between light convergence–divergence and the slope of emergent light,combined with the relationship between a natural logarithm and growth in physical reality and the second derivative of a function in practical significance,we determine the boundary point between RRC and RSC,namely,the inflection point. From such a perspective,a photonic nanojet (PNJ) and near-field focusing by light irradiation on RSC and RRC,as well as the position of the inflection point under different refractive index contrasts and the field distribution of light focusing,are studied with finite-element-method-based numerical simulation and ray-optics-based theoretical analysis. By illuminating light of different field intensity ratios to the regions divided by the inflection point,we demonstrate the generation of a photonic hook (PH) and the modulation of PNJ/PH in a new manner.
基金This work is supported by the National Key Research and Development Program of China(Scientific and Technological Innovation Cooperation of Mainland and Macao)(2017YFE0120000)the Natural Science Foundation of China(91859117,81771906,81901812,81527901,and 31870991)+4 种基金the CAS Key Laboratory of Health Informatics(2011DP173015)the Guangdong Innovative and Entrepreneurial Research Team Program(2019ZT08Y191)the Science and Technology Innovation Fund of Shenzhen(JCYJ20170818161918918 and JCYJ20190812163614809)the Shenzhen Key Laboratory of Ultrasound Imaging and Therapy(ZDSYS201802061806314)the China Postdoctoral Science Foundation(2019M653129).
文摘Fluorescence probes with aggregation-induced emission(AIE)characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution.However,the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation.Here,we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green(ICG)during a study period of 36 days to demonstrate AIE probes are nontoxic.Furthermore,through bright and nontoxic AIE probes and fluorescence imaging in the second window(NIR-II,1,000-1,700 nm),we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates,breaking the current limitation of millimeter-deep NIR-II fluorescence imaging.Our important findings,i.e.,nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates,may facilitate successful translation of AIE probes in clinical trials.
基金National Natural Science Foundation of China(62105353,81927803,82071972,91959121,92159104)Natural Science Foundation of Guangdong Province(2019A1515011746,2020B121201010,2021A1515012022)+1 种基金Scientific Instrument Innovation Team of Chinese Academy of Sciences(GJJSTD20180002)Shenzhen Basic Research Program(RCJC20200714114433058,RCYX20210609104445093,ZDSY20130401165820357)。
文摘Artificial neural networks have shown great proficiency in transforming low-resolution microscopic images into high-resolution images.However,training data remains a challenge,as large-scale open-source databases of microscopic images are rare,particularly 3D data.Moreover,the long training times and the need for expensive computational resources have become a burden to the research community.We introduced a deep-learning-based self-supervised volumetric imaging approach,which we termed“Self-Vision.”The self-supervised approach requires no training data,apart from the input image itself.The lightweight network takes just minutes to train and has demonstrated resolution-enhancing power on par with or better than that of a number of recent microscopybased models.Moreover,the high throughput power of the network enables large image inference with less postprocessing,facilitating a large field-of-view(2.45 mm×2.45 mm)using a home-built two-photon microscopy system.Self-Vision can recover images from fourfold undersampled inputs in the lateral and axial dimensions,dramatically reducing the acquisition time.Self-Vision facilitates the use of a deep neural network for 3D microscopy imaging,easing the demanding process of image acquisition and network training for current resolutionenhancing networks.
基金This work was partially supported by the University Grants Committee of Hong Kong(AoE/P-03/08)the Research Grants Council of Hong Kong(16301614,16305015,and N_HKUST604/14)the Innovation and Technology Commission(ITC-CNERC14SC01,ITS/254117,and RE:ITCPD/17-9)。
文摘Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with superior sensitivity and biological selectivity for fluorescence imaging is thus impera-tive.To move forward in this direction,we developed an easy self-assembly method for fabricating apta-mer-anchored rubrene-loaded organic fluorescent nanoprobes.The aptamer-modified organic nanop-robes integrated the best features of the organic light-emitting materials and the aptamers,thus endowing them with excellent cell-targeting capabil-ity,high stability,and good biocompatibility.By using this general method,a variety of biocompatible and highly bright organic fluorescent nanoprobes based on novel organic light-emitting materials with specific recognition could be easily constructed for real-time biosensing and long-term biomedical imaging.
