Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H ...Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.展开更多
In this study,we aimed to investigate the causal associations of brain structure with bone mineral density(BMD).Based on the genome-wide association study(GWAS)summary statistics of 1325 brain imaging-derived phenotyp...In this study,we aimed to investigate the causal associations of brain structure with bone mineral density(BMD).Based on the genome-wide association study(GWAS)summary statistics of 1325 brain imaging-derived phenotypes(BIDPs)of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations,including the total body,femoral neck,lumbar spine,forearm,and heel from the GEFOS Consortium,linkage disequilibrium score regression(LDSC)was conducted to determine the genetic correlations,and Mendelian randomization(MR)was then performed to explore the causal relationship between the BIDPs and BMD.Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes.To increase confidence in our findings,we also performed confirmatory MR between BIDPs and osteoporosis.LDSC revealed that 1.93%of BIDPs,with a false discovery rate(FDR)<0.01,were genetically correlated with BMD.Additionally,we observed that 1.31%of BIDPs exhibited a significant causal relationship with BMD(FDR<0.01)through MR.Both the LDSC and MR results demonstrated that the BIDPs“Volume of normalized brain,”“Volume of gray matter in Left Inferior Frontal Gyrus,pars opercularis,”“Volume of Estimated Total Intra Cranial”and“Volume-ratio of brain segmentation/estimated total intracranial”had strong associations with BMD.Interestingly,our results showed that more left BIDPs were causally associated with BMD,especially within and around the left frontal region.In conclusion,a part of the brain structure causally influences BMD,which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.展开更多
In this research,an atmospheric-pressure air plasma is used to inactivate the multidrug-resistant Acinetobacter baumannii in liquid.The efficacy of the air plasma on bacterial deactivation and the cytobiological varia...In this research,an atmospheric-pressure air plasma is used to inactivate the multidrug-resistant Acinetobacter baumannii in liquid.The efficacy of the air plasma on bacterial deactivation and the cytobiological variations after the plasma treatment are investigated.According to colony forming units,nearly all the bacteria(6-log) are inactivated after 10 min of air plasma treatment.However,7% of the bacteria enter a viable but non-culturable state detected by the resazurin based assay during the same period of plasma exposure.Meanwhile,86% of the bacteria lose their membrane integrity in the light of SYTO 9/PI staining assay.The morphological changes in the cells are examined by scanning electron microscopy and bacteria with morphological changes are rare after plasma exposure in the liquid.The concentrations of the long-living RS,such as H_2O_2,NO_3^- and O_3,in liquid induced by plasma treatment are measured,and they increase with plasma treatment time.The changes of the intracellular ROS may be related to cell death,which may be attributed to oxidative stress and other damage effects induced by RS plasma generated in liquid.The rapid and effective bacteria inactivation may stem from the RS in the liquid generated by plasma and air plasmas may become a valuable therapy in the treatment of infected wounds.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos.81874006,82172399,81902222,82060395,81902277,82072504,82000845)the Hunan Province Natural Science Foundation of China (Grant Nos.2020JJ4928,2020JJ4897,2021JJ30038,2021JJ40492)the Independent Exploration and Innovation Project of Central South University (Grant Nos.2020zzts255)。
文摘Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
文摘In this study,we aimed to investigate the causal associations of brain structure with bone mineral density(BMD).Based on the genome-wide association study(GWAS)summary statistics of 1325 brain imaging-derived phenotypes(BIDPs)of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations,including the total body,femoral neck,lumbar spine,forearm,and heel from the GEFOS Consortium,linkage disequilibrium score regression(LDSC)was conducted to determine the genetic correlations,and Mendelian randomization(MR)was then performed to explore the causal relationship between the BIDPs and BMD.Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes.To increase confidence in our findings,we also performed confirmatory MR between BIDPs and osteoporosis.LDSC revealed that 1.93%of BIDPs,with a false discovery rate(FDR)<0.01,were genetically correlated with BMD.Additionally,we observed that 1.31%of BIDPs exhibited a significant causal relationship with BMD(FDR<0.01)through MR.Both the LDSC and MR results demonstrated that the BIDPs“Volume of normalized brain,”“Volume of gray matter in Left Inferior Frontal Gyrus,pars opercularis,”“Volume of Estimated Total Intra Cranial”and“Volume-ratio of brain segmentation/estimated total intracranial”had strong associations with BMD.Interestingly,our results showed that more left BIDPs were causally associated with BMD,especially within and around the left frontal region.In conclusion,a part of the brain structure causally influences BMD,which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.
基金supported by the Spark Program of the second Affiliated Hospital of Anhui Medical University (Grant No.2015hhjh04)National Natural Science Foundation of China under Grant No.51777206+6 种基金Natural Science Foundation of Anhui Province (Grant No.1708085MA13 and No.1708085MB47)Science Foundation of Institute of Plasma Physics,Chinese Academy of Sciences under Grant (No.DSJJ-14-YY02)City University of Hong Kong Applied Research Grant (ARG) (No.9667144)Hong Kong Research Grants Council (RGC) General Research Funds (GRF) (No.City U 11301215)Doctoral Fund of Ministry of Education of China (No.2017M612058)Specialized Research Fund for the Doctoral Program of Hefei University of Technology (No.JZ2016HGBZ0768)Foundation of Anhui Province Key Laboratory of Medical Physics and Technology (Grant No.LMPT2017Y7BP0U1581)
文摘In this research,an atmospheric-pressure air plasma is used to inactivate the multidrug-resistant Acinetobacter baumannii in liquid.The efficacy of the air plasma on bacterial deactivation and the cytobiological variations after the plasma treatment are investigated.According to colony forming units,nearly all the bacteria(6-log) are inactivated after 10 min of air plasma treatment.However,7% of the bacteria enter a viable but non-culturable state detected by the resazurin based assay during the same period of plasma exposure.Meanwhile,86% of the bacteria lose their membrane integrity in the light of SYTO 9/PI staining assay.The morphological changes in the cells are examined by scanning electron microscopy and bacteria with morphological changes are rare after plasma exposure in the liquid.The concentrations of the long-living RS,such as H_2O_2,NO_3^- and O_3,in liquid induced by plasma treatment are measured,and they increase with plasma treatment time.The changes of the intracellular ROS may be related to cell death,which may be attributed to oxidative stress and other damage effects induced by RS plasma generated in liquid.The rapid and effective bacteria inactivation may stem from the RS in the liquid generated by plasma and air plasmas may become a valuable therapy in the treatment of infected wounds.
