Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine deriva...Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.展开更多
Computational approaches for predicting drug-target interactions(DTIs)are pivotal in advancing drug discovery.Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local an...Computational approaches for predicting drug-target interactions(DTIs)are pivotal in advancing drug discovery.Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information.To comprehensively consider network information,we propose DHGT-DTI,a novel deep learning-based approach for DTI prediction.Specifically,we capture the local and global structural information of the network from both neighborhood and meta-path per-spectives.In the neighborhood perspective,we employ a heterogeneous graph neural network(HGNN),which extends Graph Sample and Aggregate(GraphSAGE)to handle diverse node and edge types,effectively learning local network structures.In the meta-path perspective,we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths,such as"drug-disease-drug",and use an attention mechanism to fuse information across multiple meta-paths.The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method.Furthermore,DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy.Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods.Additionally,case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.展开更多
Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hundreds of ASD risk genes,implicated in synaptic forma...Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hundreds of ASD risk genes,implicated in synaptic formation and transcriptional regulation,have been identified through human genetic studies,the East Asian ASD cohorts are still under-represented in genome-wide genetic studies.Here,we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin.Using a joint-calling analytical pipeline based on GATK toolkits,we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants,as well as de novo copy number variations containing known ASD-related genes.Importantly,combined with single-cell sequencing data from the developing human brain,we found that the expression of genes with de novo mutations was specifically enriched in the pre-,post-central gyrus(PRC,PC)and banks of the superior temporal(BST)regions in the human brain.By further analyzing the brain imaging data with ASD and healthy controls,we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls,suggesting the potential structural deficits associated with ASD.Finally,we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas,the insula,as well as the frontal lobes in ASD patients.This work indicated that combinatorial analysis with genome-wide screening,single-cell sequencing,and brain imaging data reveal the brain regions contributing to the etiology of ASD.展开更多
Ammonia has emerged as a promising energy carrier owing to its carbon neutral content and low expense in long-range transportation.Therefore,development of a specific pathway to release the energy stored in ammonia is...Ammonia has emerged as a promising energy carrier owing to its carbon neutral content and low expense in long-range transportation.Therefore,development of a specific pathway to release the energy stored in ammonia is therefore in urgent demand.Electrochemical oxidation provides a convenient and reliable route to attain efficient utilization of ammonia.Here,we report that the high entropy(Mn,Fe,Co,Ni,Cu)_(3)O_(4)oxides can achieve high electrocatalytic activity for ammonia oxidation reaction(AOR)in non-aqueous solutions.The AOR onset overpotential of(Mn,Fe,Co,Ni,Cu)_(3)O_(4)is 0.70 V,which is nearly 0.2 V lower than that of their most active single metal cation counterpart.The mass spectroscopy study reveals that(Mn,Fe,Co,Ni,Cu)_(3)O_(4)preferentially oxidizes ammonia to environmentally friendly diatomic nitrogen with a Faradic efficiency of over 85%.The Xray photoelectron spectroscopy(XPS)result indicates that the balancing metal d-band of Mn and Cu cations helps retain a longlasting electrocatalytic activity.Overall,this work introduces a new family of earth-abundant transition metal high entropy oxide electrocatalysts for AOR,thus heralding a new paradigm of catalyst design for enabling ammonia as an energy carrier.展开更多
Stem cells are undifferentiated cells capable of self-renewal and differentiation,giving rise to specialized functional cells.Stem cells are of pivotal importance for organ and tissue development,homeostasis,and injur...Stem cells are undifferentiated cells capable of self-renewal and differentiation,giving rise to specialized functional cells.Stem cells are of pivotal importance for organ and tissue development,homeostasis,and injury and disease repair.Tissue-specific stem cells are a rare population residing in specific tissues and present powerful potential for regeneration when required.They are usually named based on the resident tissue,such as hematopoietic stem cells and germline stem cells.This review discusses the recent advances in stem cells of various tissues,including neural stem cells,muscle stem cells,liver progenitors,pancreatic islet stem/progenitor cells,intestinal stem cells,and prostate stem cells,and the future perspectives for tissue stem cell research.展开更多
Background Proteins containing the Jumonji C(JmjC)domain participated in tumorigenesis and cancer progression.However,the mechanisms underlying this effect are still poorly understood.Our objective was to investigate ...Background Proteins containing the Jumonji C(JmjC)domain participated in tumorigenesis and cancer progression.However,the mechanisms underlying this effect are still poorly understood.Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2(JARID2)—a JmjC family protein—in breast cancer,as well as its latent association with obesity.Methods Immunohistochemistry,The Cancer Genome Atlas,Gene Expression Omnibus,and other databases were used to analyze the expression of JARID2 in breast cancer cells.Growth curve,5-ethynyl-2-deoxyuridine(EdU),colony formation,and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion.Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness.RNA-sequencing,Kyoto Encyclopedia of Genes and Genomes,and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates.Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2.The results were further verified using co-immunoprecipitation and glutathione S-transferase(GST)pull-down experiments.Using chromatin immunoprecipitation(ChIP)sequencing,we sought the target genes that JARID2 and metastasis-associated protein 1(MTA1)jointly regulated;the results were validated by ChIP-PCR,quantitative ChIP(qChIP)and ChIP-reChIP assays.A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes.Results In this study,we found that JARID2 was highly expressed in multiple types of cancer including breast cancer.JARID2 promoted glycolysis,lipid metabolism,proliferation,invasion,and stemness of breast cancer cells.Furthermore,JARID2 physically interacted with the nucleosome remodeling and deacetylase(NuRD)complex,transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated(BRCA2),RB transcriptional corepressor 1(RB1),and inositol polyphosphate-4-phosphatase type II B(INPP4B).Additionally,JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in the breast cancer microenvironment.Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer.Conclusion Our data indicated that JARID2 promoted breast tumorigenesis and development,confirming JARID2 as a target for cancer treatment.展开更多
Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of comp...Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of composite lattice structures with different strut radius that consist of simple cubic(structure A),body-centered cubic(structure B),and edge-centered cubic(structure C)unit cells are designed.The designed structures are firstly simulated and analysed by the finite element(FE)method.Commercially pure Ti(CP-Ti)lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting(SLM),and the dimensions,microtopography,and mechanical properties are characterised.The results show that among the six types of composite lattice structures,combined BA,CA,and CB structures exhibit smaller maximum von-Mises stress,indicating that these structures have higher strength.Based on the fitting curves of stress/specific surface area versus strut radius,the optimized strut radius of BA,CA,and CB structures is 0.28,0.23,and 0.30 mm respectively.Their corresponding compressive yield strength and compressive modulus are 42.28,30.11,and 176.96 MPa,and 4.13,2.16,and 7.84 GPa,respectively.The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone,which makes it a potential candidate for subchondral bone restorations.展开更多
Vision formation is classically based on projections from retinal ganglion cells(RGC)to the lateral geniculate nucleus(LGN)and the primary visual cortex(V1).Neurons in the mouse V1 are tuned to light stimuli.Although ...Vision formation is classically based on projections from retinal ganglion cells(RGC)to the lateral geniculate nucleus(LGN)and the primary visual cortex(V1).Neurons in the mouse V1 are tuned to light stimuli.Although the cellular information of the retina and the LGN has been widely studied,the transcriptome profiles of single light-stimulated neuron in V1 remain unknown.In our study,in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as lightsensitive(LS)or non-light-sensitive(NS)by single-cell light-evoked calcium evaluation and action potential spiking.The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing.Moreover,the three-dimensional(3-D)morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings.Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation,such as Rtn4r and Rgs7,and genes involved in membrane transport,such as Na+/K+ATPase and NMDA-type glutamatergic receptors,preferentially responded to light stimulation.Furthermore,an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice.In conclusion,our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.展开更多
The concurrent implementation of cascade reactions that combine biocatalysis and chemocatalysis is a challenging undertaking.Electrocatalysis provides versatile catalytic abilities and allows for mild reaction conditi...The concurrent implementation of cascade reactions that combine biocatalysis and chemocatalysis is a challenging undertaking.Electrocatalysis provides versatile catalytic abilities and allows for mild reaction conditions,offering the potential for designing concurrent chemoenzymatic cascade reactions.The research on bioelectrocatalysis has primarily concentrated on utilizing electrocatalysis to achieve cofactor regeneration of enzymes.In contrast with previous reports,herein,we developed a deracemization strategy involving the concurrent combination of biocatalytic reduction and anodic oxidation in an undivided cell to achieve chiral sulfoxides,demonstrating the good compatibility.We anticipate this study will offer an alternative pathway for the design of the cascade reaction combined with electrocatalysis and biocatalysis.展开更多
基金financially supported by the Key R&D Special Project of Henan Province,China (241111110300)the National Natural Science Foundation of China (32402849)+2 种基金the Department of Henan Science and Technology,China (252102110035)the Doctoral Research Initiation Fund of Henan University of Animal Husbandry and Economy,China (2022HNUAHEDF033)Key Research Projects of Higher Education Institutions in Henan Province,China (25A150025)。
文摘Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.
基金the National Natural Science Foundation of China(Grant Nos.:62272288,U22A2041)Fundamental Research Funds for the Central Universities,Shaanxi Normal University(Grant No.:GK202302006)the Scientific Research Fund of Hunan Provincial Education Department of China(Grant No.:22B0097).
文摘Computational approaches for predicting drug-target interactions(DTIs)are pivotal in advancing drug discovery.Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information.To comprehensively consider network information,we propose DHGT-DTI,a novel deep learning-based approach for DTI prediction.Specifically,we capture the local and global structural information of the network from both neighborhood and meta-path per-spectives.In the neighborhood perspective,we employ a heterogeneous graph neural network(HGNN),which extends Graph Sample and Aggregate(GraphSAGE)to handle diverse node and edge types,effectively learning local network structures.In the meta-path perspective,we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths,such as"drug-disease-drug",and use an attention mechanism to fuse information across multiple meta-paths.The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method.Furthermore,DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy.Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods.Additionally,case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.
基金This work was supported by the National Natural Science Foundation of China(31625013,81941015,32000726,and 61973086)the Shanghai Brain-Intelligence Project from STCSM(16JC1420501)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDBS01060200)the Program of Shanghai Academic Research LeaderThe Open Large Infrastructure Research of the Chinese Academy of Sciences,and the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01).
文摘Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hundreds of ASD risk genes,implicated in synaptic formation and transcriptional regulation,have been identified through human genetic studies,the East Asian ASD cohorts are still under-represented in genome-wide genetic studies.Here,we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin.Using a joint-calling analytical pipeline based on GATK toolkits,we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants,as well as de novo copy number variations containing known ASD-related genes.Importantly,combined with single-cell sequencing data from the developing human brain,we found that the expression of genes with de novo mutations was specifically enriched in the pre-,post-central gyrus(PRC,PC)and banks of the superior temporal(BST)regions in the human brain.By further analyzing the brain imaging data with ASD and healthy controls,we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls,suggesting the potential structural deficits associated with ASD.Finally,we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas,the insula,as well as the frontal lobes in ASD patients.This work indicated that combinatorial analysis with genome-wide screening,single-cell sequencing,and brain imaging data reveal the brain regions contributing to the etiology of ASD.
基金supported by the Energy Research Seed Grant from Duke Energy Initiative,the National Science Foundation(Nos.CHE-1565657 and CHE-1954838)the Army Research Office(W911NFN-18-2-004)+2 种基金S.H.and P.N.are both supported by fellowships from Department of Chemistry at Duke UniversityThis work was performed in part at the Duke University Shared Materials Instrumentation Facility(SMIF),a member of the North Carolina Research Triangle Nanotechnology Network(RTNN)which is supported by the National Science Foundation(award number ECCS-2025064)as part of the National Nanotechnology Coordinated Infrastructure(NNCI).
文摘Ammonia has emerged as a promising energy carrier owing to its carbon neutral content and low expense in long-range transportation.Therefore,development of a specific pathway to release the energy stored in ammonia is therefore in urgent demand.Electrochemical oxidation provides a convenient and reliable route to attain efficient utilization of ammonia.Here,we report that the high entropy(Mn,Fe,Co,Ni,Cu)_(3)O_(4)oxides can achieve high electrocatalytic activity for ammonia oxidation reaction(AOR)in non-aqueous solutions.The AOR onset overpotential of(Mn,Fe,Co,Ni,Cu)_(3)O_(4)is 0.70 V,which is nearly 0.2 V lower than that of their most active single metal cation counterpart.The mass spectroscopy study reveals that(Mn,Fe,Co,Ni,Cu)_(3)O_(4)preferentially oxidizes ammonia to environmentally friendly diatomic nitrogen with a Faradic efficiency of over 85%.The Xray photoelectron spectroscopy(XPS)result indicates that the balancing metal d-band of Mn and Cu cations helps retain a longlasting electrocatalytic activity.Overall,this work introduces a new family of earth-abundant transition metal high entropy oxide electrocatalysts for AOR,thus heralding a new paradigm of catalyst design for enabling ammonia as an energy carrier.
基金supported by grants from the National Natural Science Foundation of China(31988101 and 31730056 to YGC32125013 and 81772723 to DG+15 种基金32170804 to PH31930030 to LH91732301,31671072,31771140,81891001,91432111,81527901,31400977,31625013 to XW31625020,31830056,31861163006 to YAZ)the Ministry of Science and Technology of China(2017YFA0103601 to YGC2020YFA0509000,2017YFA0505500 to DG2017YFA0102700 to PH2019YFA0802001,2019YFA0801503 to LH2017YFA0102601,2019YFA0110100 to XW2020YFA0509002,2019YFA0802002 to YAZ)the Strategic Priority Research Program of the Chinese Academy of Science(XDA16020400 to PHXDA16020200 to YAZ)the Shanghai Science and Technology Commission(21XD1424200,21ZR1470100 to DG)the Basic Frontier Science Research Program of Chinese Academy of Sciences(ZDBS-LY-SM015 to DG)Space Medical Experiment Project of China Manned Space Program(HYZHXM01017 to PH)the Grants of Beijing Brain Initiative of Beijing Municipal Science&Technology Commission(Z181100001518004 to XW)。
文摘Stem cells are undifferentiated cells capable of self-renewal and differentiation,giving rise to specialized functional cells.Stem cells are of pivotal importance for organ and tissue development,homeostasis,and injury and disease repair.Tissue-specific stem cells are a rare population residing in specific tissues and present powerful potential for regeneration when required.They are usually named based on the resident tissue,such as hematopoietic stem cells and germline stem cells.This review discusses the recent advances in stem cells of various tissues,including neural stem cells,muscle stem cells,liver progenitors,pancreatic islet stem/progenitor cells,intestinal stem cells,and prostate stem cells,and the future perspectives for tissue stem cell research.
基金National Natural Science Foundation of China,Grant/Award Numbers:41931291,42125707,82273403,82203820,82002993Major State Basic Research Development Program of China,Grant/Award Number:2022YFA1103402+2 种基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Numbers:2019PT310027,2021-RC310-006Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-018China Postdoctoral Science Foundation,Grant/Award Number:2022M710454。
文摘Background Proteins containing the Jumonji C(JmjC)domain participated in tumorigenesis and cancer progression.However,the mechanisms underlying this effect are still poorly understood.Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2(JARID2)—a JmjC family protein—in breast cancer,as well as its latent association with obesity.Methods Immunohistochemistry,The Cancer Genome Atlas,Gene Expression Omnibus,and other databases were used to analyze the expression of JARID2 in breast cancer cells.Growth curve,5-ethynyl-2-deoxyuridine(EdU),colony formation,and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion.Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness.RNA-sequencing,Kyoto Encyclopedia of Genes and Genomes,and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates.Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2.The results were further verified using co-immunoprecipitation and glutathione S-transferase(GST)pull-down experiments.Using chromatin immunoprecipitation(ChIP)sequencing,we sought the target genes that JARID2 and metastasis-associated protein 1(MTA1)jointly regulated;the results were validated by ChIP-PCR,quantitative ChIP(qChIP)and ChIP-reChIP assays.A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes.Results In this study,we found that JARID2 was highly expressed in multiple types of cancer including breast cancer.JARID2 promoted glycolysis,lipid metabolism,proliferation,invasion,and stemness of breast cancer cells.Furthermore,JARID2 physically interacted with the nucleosome remodeling and deacetylase(NuRD)complex,transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated(BRCA2),RB transcriptional corepressor 1(RB1),and inositol polyphosphate-4-phosphatase type II B(INPP4B).Additionally,JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in the breast cancer microenvironment.Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer.Conclusion Our data indicated that JARID2 promoted breast tumorigenesis and development,confirming JARID2 as a target for cancer treatment.
基金This research work is supported by the National Natural Science Foundation of China(51922004,51874037)State Key Lab of Advanced Metals and Materials,University of Science and Technology Beijing(2019-Z14)+4 种基金Fundamental Research Funds for the Central Universities(FRF-TP-19005C1Z)Chaozong Liu acknowledges the support from the European Commission via the H2020 MSCA RISE BAMOS programme(734156)Bo Su would like to thank the financial support from the MRC(MR/S010343/1)the EU H2020 MSCA RISE Bio-TUNE programmeWei Xu acknowledges the support from the China Scholarship Council(CSC)for a CSC Ph.D.scholarship(201906460106).
文摘Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of composite lattice structures with different strut radius that consist of simple cubic(structure A),body-centered cubic(structure B),and edge-centered cubic(structure C)unit cells are designed.The designed structures are firstly simulated and analysed by the finite element(FE)method.Commercially pure Ti(CP-Ti)lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting(SLM),and the dimensions,microtopography,and mechanical properties are characterised.The results show that among the six types of composite lattice structures,combined BA,CA,and CB structures exhibit smaller maximum von-Mises stress,indicating that these structures have higher strength.Based on the fitting curves of stress/specific surface area versus strut radius,the optimized strut radius of BA,CA,and CB structures is 0.28,0.23,and 0.30 mm respectively.Their corresponding compressive yield strength and compressive modulus are 42.28,30.11,and 176.96 MPa,and 4.13,2.16,and 7.84 GPa,respectively.The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone,which makes it a potential candidate for subchondral bone restorations.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)National Basic Research Program of China(2019YFA0110101,2017YFA0103303,2017YFA0102601)+2 种基金the National Natural Science Foundation of China(NSFC)(31671072,31771140,81891001)the Beijing Brain Initiative of Beijing Municipal Science&Technology Commission(Z181100001518004)Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning.
文摘Vision formation is classically based on projections from retinal ganglion cells(RGC)to the lateral geniculate nucleus(LGN)and the primary visual cortex(V1).Neurons in the mouse V1 are tuned to light stimuli.Although the cellular information of the retina and the LGN has been widely studied,the transcriptome profiles of single light-stimulated neuron in V1 remain unknown.In our study,in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as lightsensitive(LS)or non-light-sensitive(NS)by single-cell light-evoked calcium evaluation and action potential spiking.The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing.Moreover,the three-dimensional(3-D)morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings.Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation,such as Rtn4r and Rgs7,and genes involved in membrane transport,such as Na+/K+ATPase and NMDA-type glutamatergic receptors,preferentially responded to light stimulation.Furthermore,an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice.In conclusion,our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.
基金funded by the National Natural Science Foundation of China(Nos.22322705,22171243,22301276)National Key Research and Development Program of China(No.2021YFC2102000)+1 种基金Zhejiang Provincial Natural Science Foundation of China(No.LQ24B020009)Scientific Research Starting Foundation of Zhejiang University of Technology(No.2020105009029).
文摘The concurrent implementation of cascade reactions that combine biocatalysis and chemocatalysis is a challenging undertaking.Electrocatalysis provides versatile catalytic abilities and allows for mild reaction conditions,offering the potential for designing concurrent chemoenzymatic cascade reactions.The research on bioelectrocatalysis has primarily concentrated on utilizing electrocatalysis to achieve cofactor regeneration of enzymes.In contrast with previous reports,herein,we developed a deracemization strategy involving the concurrent combination of biocatalytic reduction and anodic oxidation in an undivided cell to achieve chiral sulfoxides,demonstrating the good compatibility.We anticipate this study will offer an alternative pathway for the design of the cascade reaction combined with electrocatalysis and biocatalysis.
