Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we use...Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.展开更多
Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treat...Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.展开更多
Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironmen...Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.展开更多
Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult ne...Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.展开更多
In this report,we present multiparameter deformability cytometry(m-DC),in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives.m-DC utilizes microflu...In this report,we present multiparameter deformability cytometry(m-DC),in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives.m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters.Parameters extracted from videos include size,deformability,deformation kinetics,and morphology.We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells,mesenchymal stem cells,neural stem cells,and their derivatives compared to size and deformability alone.In addition,we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation.This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner.Ultimately,such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.展开更多
Genetic labeling techniques allow for noninvasive lineage tracing of cells in vivo.Two-photon inducible activators provide spatial resolution for superficial cells,but labeling cells located deep within tissues is pre...Genetic labeling techniques allow for noninvasive lineage tracing of cells in vivo.Two-photon inducible activators provide spatial resolution for superficial cells,but labeling cells located deep within tissues is precluded by scattering of the far-red illumination required for two-photon photolysis.Three-photon illumination has been shown to overcome the limitations of two-photon microscopy for in vivo imaging of deep structures,but whether it can be used for photoactivation remains to be tested.Here we show,both theoretically and experimentally,that three-photon illumination overcomes scattering problems by combining longer wavelength excitation with high uncaging three-photon cross-section molecules.We prospectively labeled heart muscle cells in zebrafish embryos and found permanent labeling in their progeny in adult animals with negligible tissue damage.This technique allows for a noninvasive genetic manipulation in vivo with spatial,temporal and cell-type specificity,and may have wide applicability in experimental biology.展开更多
The authors regret that the author(A.H.)was removed as an agreement could not be reached between the two affiliations of the author.The authors would like to apologise for any inconvenience caused.
Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel wi...Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.展开更多
Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present uni...Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones,and thus are highly desired.The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature.In this review,we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine.We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts.As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites,the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites.The inorganic particles that are covered in this review are categorised into two broad types(1)solid(e.g.,calcium phosphate,hydroxyapatite,etc.)and(2)porous particles(e.g.,mesoporous silica,porous silicon etc.),which are elaborated in detail with recent examples.The review also covers other new types of inorganic material(e.g.,2D inorganic materials,clays,etc.)based polymer composites for tissue engineering applications.Lastly,we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.展开更多
Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving tech...Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving technology in molecular biology such as high-throughput sequencing and integrative analysis of genomic and transcriptomic landscapes have enabled the identification of key oncogenic events for prostate cancer initiation, progression and resistance to hormonal therapy. These surging data of prostate cancer genome also provide insights on ethnic variation and the differences in histological subtype of this disease. In this review, differences in the incidence of prostate cancer and the prevalence of main genetic alterations between Asian and Western populations are discussed. We also review the recent findings on the mechanisms underlying neuroendocrine differentiation of prostate cancer and the development of small cell neuroendocrine carcinoma after androgen deprivation therapy.展开更多
Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of ...Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of mesoporous silica rods with large cone-shaped pores(MSR-CP)to load and deliver large protein drugs.It is noted that those cone-shaped pores on the surface modulated the immune response and reduced the pro-inflammatory reaction of stimulated macrophage.Furthermore,bone morphogenetic proteins 2(BMP-2)loaded MSR-CP facilitated osteogenic differentiation and promoted osteogenesis of bone marrow stromal cells.In vivo tests confirmed BMP-2 loaded MSR-CP improved the bone regeneration performance.This study provides a potential strategy for the design of drug delivery systems for bone regeneration.展开更多
The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and ...The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and the physicochemical properties of metal organic frameworks(MOFs),we prepared nanosized zinc-based MOF:Zn-BTC with the ability to slowly release Zn^(2+).In cellular levels,Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration.It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4%MRSA and 47.2%Escherichia coli.In addition,Zn-BTC also displayed the ability of lowering the expression of antioxidant genes:superoxide dismutase 1,superoxide dismutase 2 and interleukin 6,and enhancing the expression of wound healing genes:transforming growth factors-b and type I collagen.Finally,it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs.The favorable biocompatibility,antibacterial and anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.展开更多
Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substan...Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate analysis.Several tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data;however, key quality control(QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data,including reads under peak ratio(RUPr), background(BG), promoter enrichment(Pro En), subsampling enrichment(Sub En), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package(AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity(20%–60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed q ATACViewer for the userfriendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://github.com/Zhang-lab/ATAC-seq_QC_analysis.展开更多
Excessive cell-free DNA(cfDNA)released by damaged or apoptotic cells can cause inflammation,impacting the progression of rheumatoid arthritis(RA).cfDNA scavengers,such as cationic nanoparticles(NPs),have been demonstr...Excessive cell-free DNA(cfDNA)released by damaged or apoptotic cells can cause inflammation,impacting the progression of rheumatoid arthritis(RA).cfDNA scavengers,such as cationic nanoparticles(NPs),have been demonstrated as an efficient strategy for treating RA.However,most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy.Herein,by exploiting the favorable biocompatibility,biodegradability and bioadhesion of polydopamine(P),we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy.Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity,which effectively inhibited lipopolysaccharide(LPS)stimulated inflammation in vitro,resulting in the relief of joint swelling,synovial hyperplasia and cartilage destruction in RA rats.Significantly,DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity,leading to excellent RA therapeutic effect among all of the treated groups,which was even close to normal rats.These finding provides a novel strategy for the treatment of cfDNA-associated diseases.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173 (both to ML)。
文摘Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.
基金supported by the National Natural Science Funding of China(81701032,81871503)the Wenzhou Science and Technology Association Project,the Wenzhou Major Scientific and Technological Innovation Key Medical and Health Project(ZY2019010)+4 种基金the Wenzhou Medical University grant(QTJ16026)Wenzhou Science and Technology Association Project,Wenzhou Basic Research Project(Y20180131)Zhejiang Province Program of the Medical and Health Science and Technology(2018KY537)Zhejiang Natural Science Foundation(LGF18C100002)Zhejiang Xinmiao Talents Program(2018R413186).
文摘Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.
基金This work was supported by the National Natural Science Foundation of China(Grant No.:NSFC 81871493,81871503)the Medical Science Advancement Program(Clinical Medicine)of Wuhan University(Grant No.:TFLC2018002,2018003)。
文摘Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.
基金This study was partly funded by a grant the National Natural Science Foundation of China(81802235,81871503),Zhejiang Medical and Health Science and Technology Plan Project(2021KY212),and Wenzhou Basic Science Research Plan Project(Y2020050),Advanced Postdoctoral Programs of Zhejiang(zj2019030),China Postdoctoral Science Foundation(2019M662015),CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.
基金We acknowledge financial support from the Packard Foundation and the National Science Foundation grant no.1150588.
文摘In this report,we present multiparameter deformability cytometry(m-DC),in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives.m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters.Parameters extracted from videos include size,deformability,deformation kinetics,and morphology.We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells,mesenchymal stem cells,neural stem cells,and their derivatives compared to size and deformability alone.In addition,we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation.This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner.Ultimately,such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.
基金supported by a pre-doctoral fellowship from MINECO and the I3 program,respectivelysupport was provided by grants from MINECO(SAF2012-33526,SAF2015-69706-R and BFU2012-38146)+3 种基金ISCIII/FEDER(Red de Terapia Celular—TerCel RD12/0019/0019)AGAUR(2014-SGR-1460)FundacióLa Maratóde TV3(201534-30)ERC(Grant Agreement 242993).
文摘Genetic labeling techniques allow for noninvasive lineage tracing of cells in vivo.Two-photon inducible activators provide spatial resolution for superficial cells,but labeling cells located deep within tissues is precluded by scattering of the far-red illumination required for two-photon photolysis.Three-photon illumination has been shown to overcome the limitations of two-photon microscopy for in vivo imaging of deep structures,but whether it can be used for photoactivation remains to be tested.Here we show,both theoretically and experimentally,that three-photon illumination overcomes scattering problems by combining longer wavelength excitation with high uncaging three-photon cross-section molecules.We prospectively labeled heart muscle cells in zebrafish embryos and found permanent labeling in their progeny in adult animals with negligible tissue damage.This technique allows for a noninvasive genetic manipulation in vivo with spatial,temporal and cell-type specificity,and may have wide applicability in experimental biology.
文摘The authors regret that the author(A.H.)was removed as an agreement could not be reached between the two affiliations of the author.The authors would like to apologise for any inconvenience caused.
基金This study was partly funded by grants from the National Natural Science Funding of China(82172424,82271629)Outstanding Youth Fund of Zhejiang Province(LR22H060002)+2 种基金Zhejiang Medical and Health Science and Technology Plan Project(2022RC210,2021KY212)Wenzhou Basic Science Research Plan Project(Y20210045)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.
基金the support from the National Health and Medical Research Council of Australia(NHMRC)for Early Career Fellowship(GNT1143296)the University of New South Wales for support and Scientia Grant.Q.Y.acknowledges the support Key R&D Program of China(2022YFC2504200,2022BCA029 of Hubei)the Research and Development Office,Ministry of Education-Saudi Arabia for the International Collaboration Initiative grant(#5011).
文摘Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones,and thus are highly desired.The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature.In this review,we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine.We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts.As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites,the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites.The inorganic particles that are covered in this review are categorised into two broad types(1)solid(e.g.,calcium phosphate,hydroxyapatite,etc.)and(2)porous particles(e.g.,mesoporous silica,porous silicon etc.),which are elaborated in detail with recent examples.The review also covers other new types of inorganic material(e.g.,2D inorganic materials,clays,etc.)based polymer composites for tissue engineering applications.Lastly,we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.
基金supported by the Prostate Cancer Foundationthe Broad Stem Cell Research Center at University of California, Los Angeles+5 种基金supported by the Department of Defense Prostate Cancer Research Program W81XWH-11-1-0227 (PI: Jiaoti Huang)W81XWH-12-1-0206 (PI: Lily Wu)UCLA SPORE in prostate cancer (PI: Robert Reiter)NCI 1R01CA158627 (PI: Leonard Marks)Stand-up-to-Cancer Dream Team Award (PI: Small and Witte)Prostate Cancer Foundation Honorable A. David Mazzone Special Challenge Award (PI: Robert Reiter)
文摘Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving technology in molecular biology such as high-throughput sequencing and integrative analysis of genomic and transcriptomic landscapes have enabled the identification of key oncogenic events for prostate cancer initiation, progression and resistance to hormonal therapy. These surging data of prostate cancer genome also provide insights on ethnic variation and the differences in histological subtype of this disease. In this review, differences in the incidence of prostate cancer and the prevalence of main genetic alterations between Asian and Western populations are discussed. We also review the recent findings on the mechanisms underlying neuroendocrine differentiation of prostate cancer and the development of small cell neuroendocrine carcinoma after androgen deprivation therapy.
基金The authors acknowledge the support from UQ Early Career Researcher Grant(1717673)the National Natural Science Foundation of China(Nos.81871503 and 81701032)+2 种基金C.X.acknowledges the support of National Health&Medical Research Council of Australia(NHMRC)Early Career FellowshipY.H.,L.X.and C.L.extended their appreciations to the support of Advanced QueenslandThe authors acknowledge the support from the Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy and Microanalysis,the University of Queensland.
文摘Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of mesoporous silica rods with large cone-shaped pores(MSR-CP)to load and deliver large protein drugs.It is noted that those cone-shaped pores on the surface modulated the immune response and reduced the pro-inflammatory reaction of stimulated macrophage.Furthermore,bone morphogenetic proteins 2(BMP-2)loaded MSR-CP facilitated osteogenic differentiation and promoted osteogenesis of bone marrow stromal cells.In vivo tests confirmed BMP-2 loaded MSR-CP improved the bone regeneration performance.This study provides a potential strategy for the design of drug delivery systems for bone regeneration.
基金supported by National Natural Science Foundation of China(Grant No.82160430)the Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD21075002,GuikeAD19254003)+2 种基金the Guangxi Scientific Research and Technological Development Foundation(Grant No.GuikeAB21220062)the Natural Science Foundation of Guangxi(Grant No.2020GXNSFAA159134)the Nanning Qingxiu District Science and Technology Major Special Project(Grant No.2020013).
文摘The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and the physicochemical properties of metal organic frameworks(MOFs),we prepared nanosized zinc-based MOF:Zn-BTC with the ability to slowly release Zn^(2+).In cellular levels,Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration.It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4%MRSA and 47.2%Escherichia coli.In addition,Zn-BTC also displayed the ability of lowering the expression of antioxidant genes:superoxide dismutase 1,superoxide dismutase 2 and interleukin 6,and enhancing the expression of wound healing genes:transforming growth factors-b and type I collagen.Finally,it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs.The favorable biocompatibility,antibacterial and anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.
基金supported by the National Natural Science Foundation of China(82161148008 and 81971501)the National Key Research and Development Program of China(2021YFC2301400,2020YFA0708103,and 2021YFC0863300)the Excellent Young Scientist Program of the National Natural Science Foundation of China(81822040)。
基金supported by the National Institutes of Health(Grant Nos.U24ES026699,U01HG009391,and R25DA027995)the Goldman Sachs Philanthropy Fund(Emerson Collective)Chan Zuckerberg Initiative,United States。
文摘Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate analysis.Several tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data;however, key quality control(QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data,including reads under peak ratio(RUPr), background(BG), promoter enrichment(Pro En), subsampling enrichment(Sub En), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package(AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity(20%–60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed q ATACViewer for the userfriendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://github.com/Zhang-lab/ATAC-seq_QC_analysis.
基金the National Natural Science Foundation of China(Grant No.82160430,81972120 and 82160188)the Natural Science Foundation of Guangxi(Grant No.2020GXNSFAA159134)the Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD21075002 and GuikeAD19254003).
文摘Excessive cell-free DNA(cfDNA)released by damaged or apoptotic cells can cause inflammation,impacting the progression of rheumatoid arthritis(RA).cfDNA scavengers,such as cationic nanoparticles(NPs),have been demonstrated as an efficient strategy for treating RA.However,most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy.Herein,by exploiting the favorable biocompatibility,biodegradability and bioadhesion of polydopamine(P),we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy.Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity,which effectively inhibited lipopolysaccharide(LPS)stimulated inflammation in vitro,resulting in the relief of joint swelling,synovial hyperplasia and cartilage destruction in RA rats.Significantly,DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity,leading to excellent RA therapeutic effect among all of the treated groups,which was even close to normal rats.These finding provides a novel strategy for the treatment of cfDNA-associated diseases.
