Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and geneti...Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
Flowrate control in flexible bioelectronics with targeted drug delivery capabilities is essential to ensure timely and safe delivery.For neuroscience and pharmacogenetics studies in small animals,these flexible bioele...Flowrate control in flexible bioelectronics with targeted drug delivery capabilities is essential to ensure timely and safe delivery.For neuroscience and pharmacogenetics studies in small animals,these flexible bioelectronic systems can be tailored to deliver small drug volumes on a controlled fashion without damaging surrounding tissues from stresses induced by excessively high flowrates.The drug delivery process is realized by an electrochemical reaction that pressurizes the internal bioelectronic chambers to deform a flexible polymer membrane that pumps the drug through a network of microchannels implanted in the small animal.The flowrate temporal profile and global maximum are governed and can be modeled by the ideal gas law.Here,we obtain an analytical solution that groups the relevant mechanical,fluidic,environmental,and electrochemical terms involved in the drug delivery process into a set of three nondimensional parameters.The unique combinations of these three nondimensional parameters(related to the initial pressure,initial gas volume,and microfluidic resistance)can be used to model the flowrate and scale up the flexible bioelectronic design for experiments in medium and large animal models.The analytical solution is divided into(1)a fast variable that controls the maximum flowrate and(2)a slow variable that models the temporal profile.Together,the two variables detail the complete drug delivery process and control using the three nondimensional parameters.Comparison of the analytical model with alternative numerical models shows excellent agreement and validates the analytic modeling approach.These findings serve as a theoretical framework to design and optimize future flexible bioelectronic systems used in biomedical research,or related medical fields,and analytically control the flowrate and its global maximum for successful drug delivery.展开更多
Rapid development of artificial intelligence requires the implementation of hardware systems with bioinspired parallel information processing and presentation and energy efficiency.Electrolyte-gated organic transistor...Rapid development of artificial intelligence requires the implementation of hardware systems with bioinspired parallel information processing and presentation and energy efficiency.Electrolyte-gated organic transistors(EGOTs)offer significant advantages as neuromorphic devices due to their ultra-low operation voltages,minimal hardwired connectivity,and similar operation environment as electrophysiology.Meanwhile,ionic–electronic coupling and the relatively low elastic moduli of organic channel materials make EGOTs suitable for interfacing with biology.This review presents an overview of the device architectures based on organic electrochemical transistors and organic field-effect transistors.Furthermore,we review the requirements of low energy consumption and tunable synaptic plasticity of EGOTs in emulating biological synapses and how they are affected by the organic materials,electrolyte,architecture,and operation mechanism.In addition,we summarize the basic operation principle of biological sensory systems and the recent progress of EGOTs as a building block in artificial systems.Finally,the current challenges and future development of the organic neuromorphic devices are discussed.展开更多
The emerging messenger RNA(mRNA)nanomedicines have sprung up for disease treatment.Developing targeted mRNA nanomedicines has become a thrilling research hotspot in recent years,as they can be precisely delivered to s...The emerging messenger RNA(mRNA)nanomedicines have sprung up for disease treatment.Developing targeted mRNA nanomedicines has become a thrilling research hotspot in recent years,as they can be precisely delivered to specific organs or tissues to enhance efficiency and avoid side effects.Herein,we give a comprehensive review on the latest research progress of mRNA nanomedicines with targeting functions.mRNA and its carriers are first described in detail.Then,mechanisms of passive targeting,endogenous targeting,and active targeting are outlined,with a focus on various biological barriers that mRNA may encounter during in vivo delivery.Next,emphasis is placed on summarizing mRNA-based organtargeting strategies.Lastly,the advantages and challenges of mRNA nanomedicines in clinical translation are mentioned.This review is expected to inspire researchers in this field and drive further development of mRNA targeting technology.展开更多
The blood-brain barrier(BBB)is a substantial impediment to effectively delivering central nervous system(CNS)therapies.In this review,we provide a compre-hensive dissection of the BBB's elaborate structure and fun...The blood-brain barrier(BBB)is a substantial impediment to effectively delivering central nervous system(CNS)therapies.In this review,we provide a compre-hensive dissection of the BBB's elaborate structure and function and discuss the inherent limitations of conventional dnug delivery mechanisms due to its imper-meability.We summarized the creativedeployment of nanocarriers,the astute modification of small molecules to bolster theirCNS penetration capabilities as well as the burgeoning potential of magnetic nanoparticles and optical techniques that are positioned to enable more precise and targeted drug delivery across the BBB and we discuss the current clinical application of some nanomedicines.In addition,we emphasize the indispensable role of artificial intelligence in designing novel materials and the paramount significance of interdisciplinaryresearch in surmounting clinical challenges associated withBBBpenetration.Our review meticulously integrates these insights to accentuate the impact of nano-technological innovations in BBB research and CNS disease management.It presents a promising trajectory for the evolution of patient care in neurological disorders and suggests that these scientific strides could lead to more efficacious treatments and improved outcomes for those afflicted with such conditions.展开更多
Aging and regeneration represent complex biological phenomena that have long captivated the scientific community.To fully comprehend these processes,it is essential to investigate molecular dynamics through a lens tha...Aging and regeneration represent complex biological phenomena that have long captivated the scientific community.To fully comprehend these processes,it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions.Conventional omics methodologies,such as genomics and transcriptomics,have been instrumental in identifying critical molecular facets of aging and regeneration.However,these methods are somewhat limited,constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations.The advent of emerging spatiotemporal multi-omics approaches,encompassing transcriptomics,proteomics,metabolomics,and epigenomics,furnishes comprehensive insights into these intricate molecular dynamics.These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells,tissues,and organs,thereby offering an in-depth understanding of the fundamental mechanisms at play.This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research.It underscores how these methodologies augment our comprehension of molecular dynamics,cellular interactions,and signaling pathways.Initially,the review delineates the foundational principles underpinning these methods,followed by an evaluation of their recent applications within the field.The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field.Indubitably,spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration,thus charting a course toward potential therapeutic innovations.展开更多
Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal ...Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal transduction for the regulation of host physiological activities.Microbial-regulated bile acid metabolism has been proven to affect many diseases,but there have not been many studies of disease regulation by microbial receptor signaling pathways.This review considers findings of recent research on the core roles of farnesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5),and vitamin D receptor(VDR)signaling pathways in microbial–host interactions in health and disease.Studying the relationship between these pathways can help us understand the pathogenesis of human diseases,and lead to new solutions for their treatments.展开更多
Peroxidase-like catalytic properties of Fe3O4 nanoparficles （NPs） with three different sizes, synthesized by chemical coprecipitation and sol-gel methods, were investigated by UV-vis spectrum analysis. By comparing ...Peroxidase-like catalytic properties of Fe3O4 nanoparficles （NPs） with three different sizes, synthesized by chemical coprecipitation and sol-gel methods, were investigated by UV-vis spectrum analysis. By comparing Fe3O4 NPs with average diameters of 11, 20, and 150 nm, we found that the catalytic activity increases with the reduced nanoparticle size. The electrochemical method to characterize the catalytic activity of Fe3O4 NPs using the response currents of the reaction product and substrate was also developed.展开更多
Dear Editor, Nanosized particulate systems combining better cancer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques. The surface of the...Dear Editor, Nanosized particulate systems combining better cancer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques. The surface of these nanoscale carriers is often functionalized with biological molecules for stabilization and targeted delivery. The combinations of nano-core and associated functional molecules can cross the cell membrane [1], and the surface of nanomaterials （including coating and associated functional molecules） plays a critical role in determining the outcome of their interactions with cells [2, 3]. Studying the potential effects of nanomaterials in biological systems often requires the administration of nanoparticles into a cell culture system or into living organisms in vivo. It should be noted, however, that under such conditions nanopaticles are known to adsorb proteins from the biological system,展开更多
A rapid and simple preconcentration step applying packed-fiber solid-phase extraction columns has been investigated to vitamin B12. The extraction performance of the new method was investigated preliminarily on vitami...A rapid and simple preconcentration step applying packed-fiber solid-phase extraction columns has been investigated to vitamin B12. The extraction performance of the new method was investigated preliminarily on vitamin functional drink. The analysis used a reversed-phase C18 column, with a photo-diode array detector at 220 nm. The samples were preconcentrated with packed-fiber solid-phase extraction columns. Good linearity was observed in vitamin functional drink. The repeatability of extraction performance, expressed as relative standard deviations, was from 3.5% to 4.3%. The limit of detection （LOD） is 5 ng mL^-1 （S/N = 3）. Finally, the method had been applied for the determination of vitamin B12 in vitamin functional drink.展开更多
Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for u...Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix(ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.展开更多
Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affe...Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, muki-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique.展开更多
Stem cell therapy holds great promises in medical treatment by, e.g., replacing lost cells, re-constitute healthy cell populations and also in the use of stem cells as vehicles for factor and gene delivery. Embryonic ...Stem cell therapy holds great promises in medical treatment by, e.g., replacing lost cells, re-constitute healthy cell populations and also in the use of stem cells as vehicles for factor and gene delivery. Embryonic stem cells have rightfully attracted a large interest due to their proven capacity of differentiating into any cell type in the embryo in vivo. Tissue-specific stem ceils are however already in use in medical practice, and recently the first systematic medical trials involving human neural stem cell （NSC） therapy have been launched. There are yet many obstacles to overcome and procedures to improve. To ensure progress in the medical use of stem cells increased basic knowledge of the molecular mechanisms that govern stem cell characteristics is necessary. Here we provide a review of the literature on NSCs in various aspects of cell therapy, with the main focus on the potential of using biomaterials to control NSC characteristics, differentiation, and delivery. We summarize results from studies on the characteristics of endogenous and transplanted NSCs in rodent models of neurological and cancer diseases, and highlight recent advancements in polymer compatibility and applicability in regulating NSC state and fate. We suggest that the development of specially designed polymers, such as hydrogels, is a crucial issue to improve the outcome of stem cell therapy in the central nervous system.展开更多
C,N,S-tridoped TiO2 hollow spheres （labeled as C,N,S-THs） were synthesized using carbon spheres as template and C,N,S-tridoped TiO2 nanoparticles as building blocks. The structure and physicochemical properties of t...C,N,S-tridoped TiO2 hollow spheres （labeled as C,N,S-THs） were synthesized using carbon spheres as template and C,N,S-tridoped TiO2 nanoparticles as building blocks. The structure and physicochemical properties of the catalysts were characterized by X- ray diffraction （XRD）, scanning electron microscopy （SEM）, UV-Vis diffuse reflectance spectrum （DRS）, N2 adsorption-desorption isotherms, X-ray photoelectron spectroscopy （XPS） and Photoluminescence emission spectroscopy （PL）. The results showed that the hollow spheres had average diameter of about 200 nm and the shell thickness was about 20 nm. The tridoped TiO2 hollow spheres exhibited strong absorption in the visible-light region. C,N,S-tridoped could narrow the band gap of the THs by mixing the orbit O 2p with C 2p, N 2p and S 3p orbits and shift its optical response from ultraviolet （UV） to the visible-light region. PL analysis indicated that the electron-hole recombination rate of TiO2 hollow spheres had been effectively inhibited when doped with C, N and S elements. The photocatalytic activities of the samples were evaluated for the degradation of X-3B （Reactive Brilliant Red dye, C.I. Reactive Red 2） aqueous solution under visible-light （λ 〉 420 nm） irradiation. It was found that the C,N,S-tridoped TiO2 hollow spheres indicated higher photocatalytic activity than commercial P25 and the undoped counterpart photocatalyst.展开更多
Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiova...Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiovascular drugs,heart-onchips which are promising to replace traditional animal models have been extensively researched and developed to mimic human organ functions in vitro.The heart-on-chips mainly focus on cardiac mechanics,which is regarded as the central indicator of in vitro heart models and drug testing.Traditional methods for the detection of myocardial mechanics have been demonstrated complex and inefficient in heart-on-chips.Therefore,photonic crystal materials with unique optical properties have attracted interests and have been introduced into the heart-on-chips,developing a visualized self-reporting system for cardiomyocytes activity monitoring.In this review,photonic crystal-based heart-on-chips for biosensing are introduced,as well as the fabricationmethods and design criteria of them.The characterizations of the photonic crystal materials are classified into optical properties and structural properties,and their applications in cell culture and biosensing are further discussed.Then,several representative examples and developments of the integration of photonic crystal materials into microfluidic chips are described in detail.Finally,potentials and limitations are put forward to promote the development of the photonic crystal-based intelligent heart-on-chips.展开更多
In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth char...In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.展开更多
Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials(that is, DNA). In bone tissue, nanoscale m...Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials(that is, DNA). In bone tissue, nanoscale materials can provide scaffold for excellent tissue repair via mechanical stimulation, releasing of various loaded drugs and mediators, 3D scaffold for cell growth and differentiation of bone marrow stem cells to osteocytes. This review will therefore highlight recent advancements on tissue and nanoscale materials interaction.展开更多
With unique physical properties, chemical properties, and biological effects, magnetic nanomaterials are important functional materials in many fields. In the past decades, iron based magnetic nanomaterials have attra...With unique physical properties, chemical properties, and biological effects, magnetic nanomaterials are important functional materials in many fields. In the past decades, iron based magnetic nanomaterials have attracted much attention in the biomedicine field due to their superior magnetic properties and great potential in biomedical applications. In particular, magnetic iron oxide nanoparticles(MIONPs) have been playing a crucial role in the biomedicine field because of their diagnostic and therapeutic functions. Meanwhile, MIONPs are benign, low toxic, biocompatible, and biodegradable, so they are the only inorganic magnetic nanomaterials approved by the U.S. Food and Drug Administration(FDA) for clinical use at present. In this review, we mainly introduce the progress in the preparation of iron based magnetic nanomaterials for biomedical applications, including pure iron nanoparticles, iron-based alloy nanoparticles, and MIONPs, with a focus on MIONPs. Also, we summarize the preparation methods of MIONPs and point out the importance of their developments.展开更多
Magnetic brain stimulation has greatly contributed to the advancement of neuroscience.However,challenges remain in the power of penetration and precision of magnetic stimulation,especially in small animals.Here,a nove...Magnetic brain stimulation has greatly contributed to the advancement of neuroscience.However,challenges remain in the power of penetration and precision of magnetic stimulation,especially in small animals.Here,a novel combined magnetic stimulation system(c-MSS)was established for brain stimulation in mice.The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide(SPIO)nanodrugs to elevate local cortical susceptibility.After imaging of the SPIO nanoparticles in the left prelimbic(Pr L)cortex in mice,we determined their safety and physical characteristics.Depressive-like behavior was established in mice using a chronic unpredictable mild stress(CUMS)model.SPIO nanodrugs were then delivered precisely to the left Pr L cortex using in situ injection.A 0.1 T magnetic field(adjustable frequency)was used for magnetic stimulation(5 min/session,two sessions daily).Biomarkers representing therapeutic effects were measured before and after c-MSS intervention.Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d,combined with increased brainderived neurotrophic factor(BDNF)and inactivation of hypothalamic-pituitary-adrenal(HPA)axis function,which enhanced neuronal activity due to SPIO nanoparticle-mediated effects.The c-MSS was safe and effective,representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals,playing a bioelectric role in neural circuit regulation,including antidepressant effects in CUMS mice.This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application.展开更多
基金supported by the Belle Carnell Regenerative Neurorehabilitation Fundthe National Institutes of Health(R01NS113935 to CKF)。
文摘Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
基金R.A.acknowledges support from the National Science Foundation Graduate Research Fellowship(NSF grant number DGE-1842165)and from the Ford Foundation Predoctoral Fellowship。
文摘Flowrate control in flexible bioelectronics with targeted drug delivery capabilities is essential to ensure timely and safe delivery.For neuroscience and pharmacogenetics studies in small animals,these flexible bioelectronic systems can be tailored to deliver small drug volumes on a controlled fashion without damaging surrounding tissues from stresses induced by excessively high flowrates.The drug delivery process is realized by an electrochemical reaction that pressurizes the internal bioelectronic chambers to deform a flexible polymer membrane that pumps the drug through a network of microchannels implanted in the small animal.The flowrate temporal profile and global maximum are governed and can be modeled by the ideal gas law.Here,we obtain an analytical solution that groups the relevant mechanical,fluidic,environmental,and electrochemical terms involved in the drug delivery process into a set of three nondimensional parameters.The unique combinations of these three nondimensional parameters(related to the initial pressure,initial gas volume,and microfluidic resistance)can be used to model the flowrate and scale up the flexible bioelectronic design for experiments in medium and large animal models.The analytical solution is divided into(1)a fast variable that controls the maximum flowrate and(2)a slow variable that models the temporal profile.Together,the two variables detail the complete drug delivery process and control using the three nondimensional parameters.Comparison of the analytical model with alternative numerical models shows excellent agreement and validates the analytic modeling approach.These findings serve as a theoretical framework to design and optimize future flexible bioelectronic systems used in biomedical research,or related medical fields,and analytically control the flowrate and its global maximum for successful drug delivery.
基金financial support by the self-supporting project of Pazhou Lab(No.PZL2023ZZ0011)by National Key R&D Program of China(No.2019YFA0904801).
文摘Rapid development of artificial intelligence requires the implementation of hardware systems with bioinspired parallel information processing and presentation and energy efficiency.Electrolyte-gated organic transistors(EGOTs)offer significant advantages as neuromorphic devices due to their ultra-low operation voltages,minimal hardwired connectivity,and similar operation environment as electrophysiology.Meanwhile,ionic–electronic coupling and the relatively low elastic moduli of organic channel materials make EGOTs suitable for interfacing with biology.This review presents an overview of the device architectures based on organic electrochemical transistors and organic field-effect transistors.Furthermore,we review the requirements of low energy consumption and tunable synaptic plasticity of EGOTs in emulating biological synapses and how they are affected by the organic materials,electrolyte,architecture,and operation mechanism.In addition,we summarize the basic operation principle of biological sensory systems and the recent progress of EGOTs as a building block in artificial systems.Finally,the current challenges and future development of the organic neuromorphic devices are discussed.
基金supported by the National Key Research and Development Program of China(2022YFA1105304)the National Natural Science Foundation of China(T2225003 and 61927805)+5 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)the Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB032)the Natural Science Foundation of Jiangsu Province(BK20240223)the Project of Institute of Chinese Medicine of Nanjing University(ICM2024011)the Aid Project of Nanjing Drum Tower Hospital Health,Education&Research Foundation.
文摘The emerging messenger RNA(mRNA)nanomedicines have sprung up for disease treatment.Developing targeted mRNA nanomedicines has become a thrilling research hotspot in recent years,as they can be precisely delivered to specific organs or tissues to enhance efficiency and avoid side effects.Herein,we give a comprehensive review on the latest research progress of mRNA nanomedicines with targeting functions.mRNA and its carriers are first described in detail.Then,mechanisms of passive targeting,endogenous targeting,and active targeting are outlined,with a focus on various biological barriers that mRNA may encounter during in vivo delivery.Next,emphasis is placed on summarizing mRNA-based organtargeting strategies.Lastly,the advantages and challenges of mRNA nanomedicines in clinical translation are mentioned.This review is expected to inspire researchers in this field and drive further development of mRNA targeting technology.
基金support from National Natural Science Foundation of China(22077038 and 52325304)Wuhan Science and Technology Bureau Shuguang Project Fund(NO.2022020801020592)+1 种基金Wuhan Pulmonary Hospital Fund(NO.YNZZ2203)support of the Texas Engineering Experiment Station(TEES)through a professorship to AG-E(TEES-246413).
文摘The blood-brain barrier(BBB)is a substantial impediment to effectively delivering central nervous system(CNS)therapies.In this review,we provide a compre-hensive dissection of the BBB's elaborate structure and function and discuss the inherent limitations of conventional dnug delivery mechanisms due to its imper-meability.We summarized the creativedeployment of nanocarriers,the astute modification of small molecules to bolster theirCNS penetration capabilities as well as the burgeoning potential of magnetic nanoparticles and optical techniques that are positioned to enable more precise and targeted drug delivery across the BBB and we discuss the current clinical application of some nanomedicines.In addition,we emphasize the indispensable role of artificial intelligence in designing novel materials and the paramount significance of interdisciplinaryresearch in surmounting clinical challenges associated withBBBpenetration.Our review meticulously integrates these insights to accentuate the impact of nano-technological innovations in BBB research and CNS disease management.It presents a promising trajectory for the evolution of patient care in neurological disorders and suggests that these scientific strides could lead to more efficacious treatments and improved outcomes for those afflicted with such conditions.
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(2023R01002)the National Natural Science Foundation of China(82271629,82301790)。
文摘Aging and regeneration represent complex biological phenomena that have long captivated the scientific community.To fully comprehend these processes,it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions.Conventional omics methodologies,such as genomics and transcriptomics,have been instrumental in identifying critical molecular facets of aging and regeneration.However,these methods are somewhat limited,constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations.The advent of emerging spatiotemporal multi-omics approaches,encompassing transcriptomics,proteomics,metabolomics,and epigenomics,furnishes comprehensive insights into these intricate molecular dynamics.These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells,tissues,and organs,thereby offering an in-depth understanding of the fundamental mechanisms at play.This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research.It underscores how these methodologies augment our comprehension of molecular dynamics,cellular interactions,and signaling pathways.Initially,the review delineates the foundational principles underpinning these methods,followed by an evaluation of their recent applications within the field.The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field.Indubitably,spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration,thus charting a course toward potential therapeutic innovations.
基金Project supported by the National Key Research and Development Program of China(No.2016YFA0501602)the National Natural Science Foundation of China(Nos.61801108 and 81801478)
文摘Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal transduction for the regulation of host physiological activities.Microbial-regulated bile acid metabolism has been proven to affect many diseases,but there have not been many studies of disease regulation by microbial receptor signaling pathways.This review considers findings of recent research on the core roles of farnesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5),and vitamin D receptor(VDR)signaling pathways in microbial–host interactions in health and disease.Studying the relationship between these pathways can help us understand the pathogenesis of human diseases,and lead to new solutions for their treatments.
基金This work was supported by the National Natural Science Foundation of China （Nos. 90406023 and 60571031）；National Important Science Research Program of China （Nos. 2006CB933206 and 2006CB705606）.
文摘Peroxidase-like catalytic properties of Fe3O4 nanoparficles （NPs） with three different sizes, synthesized by chemical coprecipitation and sol-gel methods, were investigated by UV-vis spectrum analysis. By comparing Fe3O4 NPs with average diameters of 11, 20, and 150 nm, we found that the catalytic activity increases with the reduced nanoparticle size. The electrochemical method to characterize the catalytic activity of Fe3O4 NPs using the response currents of the reaction product and substrate was also developed.
文摘Dear Editor, Nanosized particulate systems combining better cancer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques. The surface of these nanoscale carriers is often functionalized with biological molecules for stabilization and targeted delivery. The combinations of nano-core and associated functional molecules can cross the cell membrane [1], and the surface of nanomaterials （including coating and associated functional molecules） plays a critical role in determining the outcome of their interactions with cells [2, 3]. Studying the potential effects of nanomaterials in biological systems often requires the administration of nanoparticles into a cell culture system or into living organisms in vivo. It should be noted, however, that under such conditions nanopaticles are known to adsorb proteins from the biological system,
基金supported by Jiangsu Science and Technology Department(No.BG2007044)Jiangsu Preventive Medicine Foundation(No.Y2006025).
文摘A rapid and simple preconcentration step applying packed-fiber solid-phase extraction columns has been investigated to vitamin B12. The extraction performance of the new method was investigated preliminarily on vitamin functional drink. The analysis used a reversed-phase C18 column, with a photo-diode array detector at 220 nm. The samples were preconcentrated with packed-fiber solid-phase extraction columns. Good linearity was observed in vitamin functional drink. The repeatability of extraction performance, expressed as relative standard deviations, was from 3.5% to 4.3%. The limit of detection （LOD） is 5 ng mL^-1 （S/N = 3）. Finally, the method had been applied for the determination of vitamin B12 in vitamin functional drink.
基金supported by NSFC (nos 61471168, 61571187,61301043,and 61527806)China Postdoctoral Science Foundation (2016T90403)the Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province [(2013)448]
文摘Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix(ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.
基金supported by the National Natural Science Foundation of China,No.90307013,90707005a grant from the Science&Technology Pillar Program of Jiangsu Province in China,No.BE2013706
文摘Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, muki-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique.
文摘Stem cell therapy holds great promises in medical treatment by, e.g., replacing lost cells, re-constitute healthy cell populations and also in the use of stem cells as vehicles for factor and gene delivery. Embryonic stem cells have rightfully attracted a large interest due to their proven capacity of differentiating into any cell type in the embryo in vivo. Tissue-specific stem ceils are however already in use in medical practice, and recently the first systematic medical trials involving human neural stem cell （NSC） therapy have been launched. There are yet many obstacles to overcome and procedures to improve. To ensure progress in the medical use of stem cells increased basic knowledge of the molecular mechanisms that govern stem cell characteristics is necessary. Here we provide a review of the literature on NSCs in various aspects of cell therapy, with the main focus on the potential of using biomaterials to control NSC characteristics, differentiation, and delivery. We summarize results from studies on the characteristics of endogenous and transplanted NSCs in rodent models of neurological and cancer diseases, and highlight recent advancements in polymer compatibility and applicability in regulating NSC state and fate. We suggest that the development of specially designed polymers, such as hydrogels, is a crucial issue to improve the outcome of stem cell therapy in the central nervous system.
基金supported by the National Natural Science Foundation of China(No.51172043)the Doctor Research Starting Fund of Jinling Institute of Technology(No.JITB-201307)the Social Developing Program of Jiangsu Province(No.BE2011797)
文摘C,N,S-tridoped TiO2 hollow spheres （labeled as C,N,S-THs） were synthesized using carbon spheres as template and C,N,S-tridoped TiO2 nanoparticles as building blocks. The structure and physicochemical properties of the catalysts were characterized by X- ray diffraction （XRD）, scanning electron microscopy （SEM）, UV-Vis diffuse reflectance spectrum （DRS）, N2 adsorption-desorption isotherms, X-ray photoelectron spectroscopy （XPS） and Photoluminescence emission spectroscopy （PL）. The results showed that the hollow spheres had average diameter of about 200 nm and the shell thickness was about 20 nm. The tridoped TiO2 hollow spheres exhibited strong absorption in the visible-light region. C,N,S-tridoped could narrow the band gap of the THs by mixing the orbit O 2p with C 2p, N 2p and S 3p orbits and shift its optical response from ultraviolet （UV） to the visible-light region. PL analysis indicated that the electron-hole recombination rate of TiO2 hollow spheres had been effectively inhibited when doped with C, N and S elements. The photocatalytic activities of the samples were evaluated for the degradation of X-3B （Reactive Brilliant Red dye, C.I. Reactive Red 2） aqueous solution under visible-light （λ 〉 420 nm） irradiation. It was found that the C,N,S-tridoped TiO2 hollow spheres indicated higher photocatalytic activity than commercial P25 and the undoped counterpart photocatalyst.
基金This work was supported by the National Natural Science Foundation of China(Grants 61927805)the Natural Science Foundation of Jiangsu(Grant No.BE2018707)the Scientific Research Foundation of Nanjing University and Drum Tower Hospital.
文摘Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiovascular drugs,heart-onchips which are promising to replace traditional animal models have been extensively researched and developed to mimic human organ functions in vitro.The heart-on-chips mainly focus on cardiac mechanics,which is regarded as the central indicator of in vitro heart models and drug testing.Traditional methods for the detection of myocardial mechanics have been demonstrated complex and inefficient in heart-on-chips.Therefore,photonic crystal materials with unique optical properties have attracted interests and have been introduced into the heart-on-chips,developing a visualized self-reporting system for cardiomyocytes activity monitoring.In this review,photonic crystal-based heart-on-chips for biosensing are introduced,as well as the fabricationmethods and design criteria of them.The characterizations of the photonic crystal materials are classified into optical properties and structural properties,and their applications in cell culture and biosensing are further discussed.Then,several representative examples and developments of the integration of photonic crystal materials into microfluidic chips are described in detail.Finally,potentials and limitations are put forward to promote the development of the photonic crystal-based intelligent heart-on-chips.
基金the National Key R&D Program of China(No.2017YFA0700500)the National Natural Science Foundation of China(No.62172202)+1 种基金the Experiment Project of ChinaManned Space Program(No.HYZHXM01019)the Fundamental Research Funds for the Central Universities from Southeast University(No.3207032101C3).
文摘In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.
基金funded by the 863 project(2015AA020502)National Natural Science Foundation of China(61401217,61527806)+1 种基金Natural Science Foundation of Jiangsu Province(BK20140900)the Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province[(2013)448]
文摘Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials(that is, DNA). In bone tissue, nanoscale materials can provide scaffold for excellent tissue repair via mechanical stimulation, releasing of various loaded drugs and mediators, 3D scaffold for cell growth and differentiation of bone marrow stem cells to osteocytes. This review will therefore highlight recent advancements on tissue and nanoscale materials interaction.
基金Sponsored by the National Natural Science Foundation of China(Grant Nos.51832001 and 31800843)the National Key Research and Development Program of China(Grant No.2017YFA0104301)the Collaborative Innovation Center of Suzhou Nano Science and Technology(Grant No.SX21400213)
文摘With unique physical properties, chemical properties, and biological effects, magnetic nanomaterials are important functional materials in many fields. In the past decades, iron based magnetic nanomaterials have attracted much attention in the biomedicine field due to their superior magnetic properties and great potential in biomedical applications. In particular, magnetic iron oxide nanoparticles(MIONPs) have been playing a crucial role in the biomedicine field because of their diagnostic and therapeutic functions. Meanwhile, MIONPs are benign, low toxic, biocompatible, and biodegradable, so they are the only inorganic magnetic nanomaterials approved by the U.S. Food and Drug Administration(FDA) for clinical use at present. In this review, we mainly introduce the progress in the preparation of iron based magnetic nanomaterials for biomedical applications, including pure iron nanoparticles, iron-based alloy nanoparticles, and MIONPs, with a focus on MIONPs. Also, we summarize the preparation methods of MIONPs and point out the importance of their developments.
基金This work was supported by grants from National Natural Science Foundation of China(81830040 to Z.J.Z.)National Key Projects for Research and Development Program of China(2016YFC1306700 to Z.J.Z.,2017YFA0104302 to N.G.,and 2017YFA0104301 to J.F.S.)Program of Excellent Talents in Medical Science of Jiangsu Province(JCRCA2016006 to Z.J.Z.)。
文摘Magnetic brain stimulation has greatly contributed to the advancement of neuroscience.However,challenges remain in the power of penetration and precision of magnetic stimulation,especially in small animals.Here,a novel combined magnetic stimulation system(c-MSS)was established for brain stimulation in mice.The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide(SPIO)nanodrugs to elevate local cortical susceptibility.After imaging of the SPIO nanoparticles in the left prelimbic(Pr L)cortex in mice,we determined their safety and physical characteristics.Depressive-like behavior was established in mice using a chronic unpredictable mild stress(CUMS)model.SPIO nanodrugs were then delivered precisely to the left Pr L cortex using in situ injection.A 0.1 T magnetic field(adjustable frequency)was used for magnetic stimulation(5 min/session,two sessions daily).Biomarkers representing therapeutic effects were measured before and after c-MSS intervention.Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d,combined with increased brainderived neurotrophic factor(BDNF)and inactivation of hypothalamic-pituitary-adrenal(HPA)axis function,which enhanced neuronal activity due to SPIO nanoparticle-mediated effects.The c-MSS was safe and effective,representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals,playing a bioelectric role in neural circuit regulation,including antidepressant effects in CUMS mice.This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application.
