Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in...Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in prophylaxis,calling for the need for drug improvement.Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms.The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments,providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies.A total of 128 sequences were obtained after sequencing 196 memory B cells,and 42 sequences were left after merging extremely similar ones and discarding incomplete ones,followed by homology modeling of the antibody variable region.Thirteen candidate sequences were expressed,of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants.The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.展开更多
Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory...Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.展开更多
Rett syndrome(RTT)is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum disorders.MeCP2 protein loss-of-function in neural lineage cells is the ma...Rett syndrome(RTT)is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum disorders.MeCP2 protein loss-of-function in neural lineage cells is the main cause of RTT pathogenicity.As it is still hard to understand the mechanism of RTT on the basis of only clinical patients or animal models,cell models cultured in vitro play indispensable roles.Here we reviewed the research progress in the pathogenesis of RTT at the cellular level,summarized the preclinical-research-related applications,and prospected potential future development.展开更多
Usually a buffer layer of cadmium sulphide is used in high efficiency solar cells based on Cu(In,Ga)Se2(CIGS). Because of cadmium toxicity, many in-vestigations have been conducted to use Cd-free buffer layers. Our wo...Usually a buffer layer of cadmium sulphide is used in high efficiency solar cells based on Cu(In,Ga)Se2(CIGS). Because of cadmium toxicity, many in-vestigations have been conducted to use Cd-free buffer layers. Our work focuses on this type of CIGS-based solar cells where CdS is replaced by a ZnS buffer layer. In this contribution, AFORS-HET software is used to simulate n-ZnO: Al/i-ZnO/n-ZnS/p-CIGS/Mo polycrystalline thin-film solar cell where the key parts are p-CIGS absorber layer and n-ZnS buffer layer. The characteristics of these key parts: thickness and Ga-content of the absorber layer, thickness of the buffer layer and doping concentrations of absorber and buffer layers have been investigated to optimize the conversion efficiency. We find a maximum conversion efficiency of 26% with a short-circuit current of 36.9 mA/cm2, an open circuit voltage of 824 mV, and a fill factor of 85.5%.展开更多
In consideration of the mechanism for shear-stress-induced Ca^2＋ influx via ATP（adenosine triphosphate）-gated ion channel P2X4 in vascular endothelial cells, a modified model is proposed to describe the shear-stres...In consideration of the mechanism for shear-stress-induced Ca^2＋ influx via ATP（adenosine triphosphate）-gated ion channel P2X4 in vascular endothelial cells, a modified model is proposed to describe the shear-stress-induced Ca^2＋ influx. It is affected both by the Ca^2＋ gradient across the cell membrane and extracellular ATP concentration on the cell surface. Meanwhile, a new static ATP release model is constructed by using published experimental data. Combining the modified intracellular calcium dynamics model with the new ATP release model, we establish a nonlinear Ca^2＋ dynamic system in vascular endothelial cells. The ATP-mediated calcium response in vascular endothelial cells subjected to shear stresses is analyzed by solving the governing equations of the integrated dynamic system. Numerical results show that the shear-stress-induced calcium response predicted by the proposed model is more consistent with the experimental observations than that predicted by existing models.展开更多
Mixed ionic electronic conductors(MIECs)have attracted increasing attention as anode materials for solid oxide fuel cells(SOFCs)and they hold great promise for lowering the operation temperature of SOFCs.However,there...Mixed ionic electronic conductors(MIECs)have attracted increasing attention as anode materials for solid oxide fuel cells(SOFCs)and they hold great promise for lowering the operation temperature of SOFCs.However,there has been a lack of understanding of the performance-limiting factors and guidelines for rational design of composite metal-MIEC electrodes.Using a newly-developed approach based on 3 D-tomography and electrochemical impedance spectroscopy,here for the first time we quantify the contribution of the dual-phase boundary(DPB)relative to the three-phase boundary(TPB)reaction pathway on real MIEC electrodes.A new design strategy is developed for Ni/gadolinium doped ceria(CGO)electrodes(a typical MIEC electrode)based on the quantitative analyses and a novel Ni/CGO fiber-matrix structure is proposed and fabricated by combining electrospinning and tape-casting methods using commercial powders.With only 11.5 vol%nickel,the designer Ni/CGO fiber-matrix electrode shows 32%and 67%lower polarization resistance than a nano-Ni impregnated CGO scaffold electrode and conventional cermet electrode respectively.The results in this paper demonstrate quantitatively using real electrode structures that enhancing DPB and hydrogen kinetics are more efficient strategies to enhance electrode performance than simply increasing TPB.展开更多
Acoustic tweezing cytometry(ATC)is a recently developed method for cell mechanics regulation.Tar-geted microbubbles,which are attached to integrins and subsequently the actin cytoskeleton,anchor,amplify and transmit t...Acoustic tweezing cytometry(ATC)is a recently developed method for cell mechanics regulation.Tar-geted microbubbles,which are attached to integrins and subsequently the actin cytoskeleton,anchor,amplify and transmit the mechanical energy in an acoustic field inside the cells,eliciting prominent cy-toskeleton contractile force increases in various cell types.We propose that a mechanochemical con-version mechanism is critical for the high efficiency of ATC to activate cell contractility responses.Our models predict key experimental observations.Moreover,we study the influences of ATC parameters(ul-trasound center frequency,pulse repetition frequency,duty cycle,and acoustic pressure),cell areas,the number of ATC stimuli,and extracellular matrix rigidity on cell contractility responses to ATC.The simu-lation results suggest that it is large molecules,rather than small ions,that facilitate global responses to the local ATC stimulation,and the incorporation of visible stress fiber bundles improves the accuracy of modeling.展开更多
Nomadic Vehicular Cloud(NVC)is envisaged in this work.The predo-minant aspects of NVC is,it moves along with the vehicle that initiates it and functions only with the resources of moving vehicles on the heavy traffic ...Nomadic Vehicular Cloud(NVC)is envisaged in this work.The predo-minant aspects of NVC is,it moves along with the vehicle that initiates it and functions only with the resources of moving vehicles on the heavy traffic road without relying on any of the static infrastructure and NVC decides the initiation time of container migration using cell transmission model(CTM).Containers are used in the place of Virtual Machines(VM),as containers’features are very apt to NVC’s dynamic environment.The specifications of 5G NR V2X PC5 interface are applied to NVC,for the feature of not relying on the network coverage.Nowa-days,the peak traffic on the road and the bottlenecks due to it are inevitable,which are seen here as the benefits for VC in terms of resource availability and residual in-network time.The speed range of high-end vehicles poses the issue of dis-connectivity among VC participants,that results the container migration failure.As the entire VC participants are on the move,to maintain proximity of the containers hosted by them,estimating their movements plays a vital role.To infer the vehicle movements on the road stretch and initiate the container migration prior enough to avoid the migration failure due to vehicles dynamicity,this paper proposes to apply the CTM to the container based and 5G NR V2X enabled NVC.The simulation results show that there is a significant increase in the success rate of vehicular cloud in terms of successful container migrations.展开更多
BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the funct...BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.展开更多
基金supported by the Jiangsu Provincial Key Research and Development Program (Grant No.BE2020616)the National Key R&D Program of China (Grant No.2018YFC1200603)+1 种基金the National Science and Technology Major Project (Grant No.2019SWAQ05-5-4)Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University.
文摘Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in prophylaxis,calling for the need for drug improvement.Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms.The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments,providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies.A total of 128 sequences were obtained after sequencing 196 memory B cells,and 42 sequences were left after merging extremely similar ones and discarding incomplete ones,followed by homology modeling of the antibody variable region.Thirteen candidate sequences were expressed,of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants.The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.
基金supported by grants awarded to YY by the National Natural Science Foundation of China (81870019, 82170029)the Guangdong Provincial Natural Science Foundation (2018A030313554)+3 种基金the Innovation Research Team for Basic and Clinical Studies on Chronic Liver Diseases of 2018 High-Level Health Teams of ZhuhaiYKQ by the National Natural Science Foundation of China (82002612)the Chinese Postdoctoral Science Foundation (2019M660211)ZGC by the Science and Technology Program of Guangzhou,China (201704020179)。
文摘Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.
基金The Major Basic Research Project of Science and Technology of YunnanGrant/Award Number:202001BC070001 and 202105AC160041+3 种基金National Natural Science Foundation of ChinaGrant/Award Number:81930121 and 31960120The National Key Research and Development Program of ChinaGrant/Award Number:2018YFA0107902 and 2018YFA0801403。
文摘Rett syndrome(RTT)is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum disorders.MeCP2 protein loss-of-function in neural lineage cells is the main cause of RTT pathogenicity.As it is still hard to understand the mechanism of RTT on the basis of only clinical patients or animal models,cell models cultured in vitro play indispensable roles.Here we reviewed the research progress in the pathogenesis of RTT at the cellular level,summarized the preclinical-research-related applications,and prospected potential future development.
文摘Usually a buffer layer of cadmium sulphide is used in high efficiency solar cells based on Cu(In,Ga)Se2(CIGS). Because of cadmium toxicity, many in-vestigations have been conducted to use Cd-free buffer layers. Our work focuses on this type of CIGS-based solar cells where CdS is replaced by a ZnS buffer layer. In this contribution, AFORS-HET software is used to simulate n-ZnO: Al/i-ZnO/n-ZnS/p-CIGS/Mo polycrystalline thin-film solar cell where the key parts are p-CIGS absorber layer and n-ZnS buffer layer. The characteristics of these key parts: thickness and Ga-content of the absorber layer, thickness of the buffer layer and doping concentrations of absorber and buffer layers have been investigated to optimize the conversion efficiency. We find a maximum conversion efficiency of 26% with a short-circuit current of 36.9 mA/cm2, an open circuit voltage of 824 mV, and a fill factor of 85.5%.
基金the National Natural Science Foundation of China(No.10472027) the NUS Academic Research Fund(No.R-263-000-483-112)
文摘In consideration of the mechanism for shear-stress-induced Ca^2＋ influx via ATP（adenosine triphosphate）-gated ion channel P2X4 in vascular endothelial cells, a modified model is proposed to describe the shear-stress-induced Ca^2＋ influx. It is affected both by the Ca^2＋ gradient across the cell membrane and extracellular ATP concentration on the cell surface. Meanwhile, a new static ATP release model is constructed by using published experimental data. Combining the modified intracellular calcium dynamics model with the new ATP release model, we establish a nonlinear Ca^2＋ dynamic system in vascular endothelial cells. The ATP-mediated calcium response in vascular endothelial cells subjected to shear stresses is analyzed by solving the governing equations of the integrated dynamic system. Numerical results show that the shear-stress-induced calcium response predicted by the proposed model is more consistent with the experimental observations than that predicted by existing models.
基金the financial support from EPSRC(EP/P024807/1,EP/M014045/1,EP/S000933/1 and EP/N009924/1)by the EPSRC energy storage for low carbon grids project(EP/K002252/1)+3 种基金the EPSRC Joint UK-India Clean Energy center(JUICE)(EP/P003605/1)the Integrated Development of Low-Carbon Energy Systems(IDLES)project(EP/R045518/1)the Innovate UK BAFTA project,the Innovate UK for Advanced Battery Lifetime Extension(ABLE)project for funding underthe China Scholarship Council。
文摘Mixed ionic electronic conductors(MIECs)have attracted increasing attention as anode materials for solid oxide fuel cells(SOFCs)and they hold great promise for lowering the operation temperature of SOFCs.However,there has been a lack of understanding of the performance-limiting factors and guidelines for rational design of composite metal-MIEC electrodes.Using a newly-developed approach based on 3 D-tomography and electrochemical impedance spectroscopy,here for the first time we quantify the contribution of the dual-phase boundary(DPB)relative to the three-phase boundary(TPB)reaction pathway on real MIEC electrodes.A new design strategy is developed for Ni/gadolinium doped ceria(CGO)electrodes(a typical MIEC electrode)based on the quantitative analyses and a novel Ni/CGO fiber-matrix structure is proposed and fabricated by combining electrospinning and tape-casting methods using commercial powders.With only 11.5 vol%nickel,the designer Ni/CGO fiber-matrix electrode shows 32%and 67%lower polarization resistance than a nano-Ni impregnated CGO scaffold electrode and conventional cermet electrode respectively.The results in this paper demonstrate quantitatively using real electrode structures that enhancing DPB and hydrogen kinetics are more efficient strategies to enhance electrode performance than simply increasing TPB.
基金This work is supported by the National Natural Science Founda-tion of China(Grant No.11874280)the State Key Laboratory of Acoustics,Chinese Academy of Sciences(Grant No.SKLA202211).
文摘Acoustic tweezing cytometry(ATC)is a recently developed method for cell mechanics regulation.Tar-geted microbubbles,which are attached to integrins and subsequently the actin cytoskeleton,anchor,amplify and transmit the mechanical energy in an acoustic field inside the cells,eliciting prominent cy-toskeleton contractile force increases in various cell types.We propose that a mechanochemical con-version mechanism is critical for the high efficiency of ATC to activate cell contractility responses.Our models predict key experimental observations.Moreover,we study the influences of ATC parameters(ul-trasound center frequency,pulse repetition frequency,duty cycle,and acoustic pressure),cell areas,the number of ATC stimuli,and extracellular matrix rigidity on cell contractility responses to ATC.The simu-lation results suggest that it is large molecules,rather than small ions,that facilitate global responses to the local ATC stimulation,and the incorporation of visible stress fiber bundles improves the accuracy of modeling.
文摘Nomadic Vehicular Cloud(NVC)is envisaged in this work.The predo-minant aspects of NVC is,it moves along with the vehicle that initiates it and functions only with the resources of moving vehicles on the heavy traffic road without relying on any of the static infrastructure and NVC decides the initiation time of container migration using cell transmission model(CTM).Containers are used in the place of Virtual Machines(VM),as containers’features are very apt to NVC’s dynamic environment.The specifications of 5G NR V2X PC5 interface are applied to NVC,for the feature of not relying on the network coverage.Nowa-days,the peak traffic on the road and the bottlenecks due to it are inevitable,which are seen here as the benefits for VC in terms of resource availability and residual in-network time.The speed range of high-end vehicles poses the issue of dis-connectivity among VC participants,that results the container migration failure.As the entire VC participants are on the move,to maintain proximity of the containers hosted by them,estimating their movements plays a vital role.To infer the vehicle movements on the road stretch and initiate the container migration prior enough to avoid the migration failure due to vehicles dynamicity,this paper proposes to apply the CTM to the container based and 5G NR V2X enabled NVC.The simulation results show that there is a significant increase in the success rate of vehicular cloud in terms of successful container migrations.
基金Supported by Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-level Hospital Construction FundShenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.
