Lipoprotein receptor-related protein 6(LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells(MSCs), skeletal stem cells that give rise to os...Lipoprotein receptor-related protein 6(LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells(MSCs), skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin1MSCs by crossing nestin-Cre mice with LRP6floxmice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin1cells demonstrated reductions in body weight and body length at 1 and 3 months of age. Bone architecture measured by microCT(mCT) showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix1osteoprogenitors and osteocalcin1osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.展开更多
Bone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function.Recently,an increasing number of studies have characterized the significa...Bone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function.Recently,an increasing number of studies have characterized the significance of bone as an endocrine organ,suggesting that bone-derived factors regulate local bone metabolism and metabolic functions.In addition,these factors can regulate global energy homeostasis by altering insulin sensitivity,feeding behavior,and adipocyte commitment.These findings may provide a new pathological mechanism for related metabolic diseases or be used in the diagnosis,treatment,and prevention of metabolic diseases such as osteoporosis,obesity,and diabetes mellitus.In this review,we summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.展开更多
The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has sho...The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration.We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA.However,the mechanism responsible for the elevation of H-type vessels in OA is still unclear.Here,we found that PDGFR-βexpression,predominantly in the CD31^(hi)Emcn^(hi) endothelium,was substantially elevated in subchondral bones from OA patients and rodent OA models.A mouse model of OA with deletion of PDGFR-βin endothelial cells(ECs)exhibited fewer H-type vessels,ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration.Endothelial PDGFR-βpromotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex.Notably,endothelium-specific inhibition of PDGFR-βby local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls.Based on the results from this study,targeting PDGFR-βis a novel and promising approach for the prevention or early treatment of OA.展开更多
Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation....Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids(oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation. We found that cell surface LRP6 in bone marrow mesenchymal stromal cells(MSCs) decreased rapidly in response to increased oxPLs in marrow microenvironment. LRP6 directly bound and mediated the uptake of oxPLs by MSCs. oxPL-LRP6 binding induced LRP6 endocytosis through a clathrin-mediated pathway, decreasing responses of MSCs to osteogenic factors and diminishing osteoblast differentiation ability. Thus, LRP6 functions as a receptor and molecular target of oxPLs for their adverse effect on MSCs, revealing a potential mechanism underlying atherosclerosis-associated bone loss.展开更多
How common reed(Phragmites australis Trin. ex Steud.) colonization correlates to soil heterogeneity and environmental determinants remains unclear in arid areas. We conducted a field investigation and soil sampling in...How common reed(Phragmites australis Trin. ex Steud.) colonization correlates to soil heterogeneity and environmental determinants remains unclear in arid areas. We conducted a field investigation and soil sampling in 100 plots along Keriya River Basin to uncover the relationship between common reed and heterogeneous soils. Reed colonization variables and its soil properties were measured and recorded for the analysis of their relationship using Pearson correlation and redundancy analysis methods. The comparison results of common reed characteristics among 100 plots showed that common reeds performed strong tolerance and ecophysiological plasticity to edaphic stresses. Common reed colonization was tightly connected to soil heterogeneity according to the correlation analysis between its colonization characteristics and soil properties. Common reed colonization got feedbacks on soil properties as well, including the increase of soil organic matter and the alleviation of salt uplifting. The main limiting environmental determinant of common reed colonization was soil salt, followed by pH and soil water content.展开更多
Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular comp...Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.展开更多
Although solar steam generation is an eco-friendly approach for desalinating seawater and purifying wastewater,there are still issues on how to improve the efficiency of solar energy utilization and accelerate the wat...Although solar steam generation is an eco-friendly approach for desalinating seawater and purifying wastewater,there are still issues on how to improve the efficiency of solar energy utilization and accelerate the water and heat transport inside the solardriven water evaporators.Herein,we design a central hollow cylindrical reduced graphene oxide(RGO)foam with vertically and radially orientated channels as a solar steam generation device for efficient water evaporation and purification.The vertically aligned porous channels accelerate upward transport of water to the top evaporation surface,while the radially aligned porous channels facilitate water transport and heat transfer along the radial directions for fully utilizing the heat accumulated inside the central cylindrical hole of the foam.The central hole of the foam plays a highly positive role in accumulating more heat for accelerating the water evaporation,the newly generated inner sidewall resulted from the central hole can gain extra thermal energy from surrounding environment in the same way as the outer sidewall of the foam due to the surface cooling effect of the water evaporation.As a result,the vertically and radially aligned RGO foam evaporator with central hollow cylinder achieves a high solar steam generation rate of 2.32 kg·m^(−2)·h^(−1)with an exceptional energy conversion efficiency of 120.9%under 1-sun irradiation,superior to the vertically aligned RGO foam without the central hole(1.83 kg·m^(−2)·h^(−1),96.9%)because of the enhanced water and heat transfer inside the porous channels,the efficient utilization of environmental energy.展开更多
Dust presented in experimental advanced superconducting tokamak(EAST)with mixed plasmafacing materials has been collected and characterized for the first time.Dust at different positions in the vessel was collected by...Dust presented in experimental advanced superconducting tokamak(EAST)with mixed plasmafacing materials has been collected and characterized for the first time.Dust at different positions in the vessel was collected by vacuum cleaner after the first experimental campaign in 2019.The shape,composition,and size of dust particles have been analyzed using different methods.About 80%of the total number of dust particles have size between 20 and 80μm,and most of dust particles are spherical,while schistose shape,columnar and irregular shape were also found.With the help of energy-dispersive x-ray spectroscopy different elements of dust have been identified,which is generally consistent with the different plasma-facing components in EAST.Both x-ray fluorescence and inductively coupled plasma emission spectrometer are complementary methods for measuring the dust composition quantitatively.It was found that the major components of dust were lithium dust in the form of lithium carbonate and lithium hydroxide,which is due to the routine lithium wall conditioning during EAST operation.展开更多
In this paper, we prove a result on the uniqueness of meromorphic functions sharing three values counting multiplicity and improve a result obtained by Xiaomin Li and Hongxun Yi.
With the increase of wind power capacity in China, the situation of curtailment of wind power is getting worse. An annual sequence production simulation model is established with maximum wind power consumption as the ...With the increase of wind power capacity in China, the situation of curtailment of wind power is getting worse. An annual sequence production simulation model is established with maximum wind power consumption as the objective function. The calculation of specific power grid operation in 2013 verifies the precision of this model. The impact of different factors on wind power accommodation as well as the impact of power grid reserve, wind resources and load on wind power curtailment is analyzed. The calculation results quantify the impact of different factors from power system to the accommodation of wind power and provide reference to solving the problem of wind power curtailment.展开更多
The establishment of self-recording precipitation observation systems in China began in 1951,and strips of self-recording precipitation graph paper have been archived since then.More than 9 million sheets of self-reco...The establishment of self-recording precipitation observation systems in China began in 1951,and strips of self-recording precipitation graph paper have been archived since then.More than 9 million sheets of self-recording graph paper from 2253 stations in 31 provinces have been digitized by using image scanning and curve extraction technology.Format specification and quality control have been applied to the digitized data,and the China Surface Self-Recording Per-Minute Precipitation Dataset(V1.0)has been developed.The integrity and accuracy of this dataset are evaluated.This is the first attempt in China to establish a per-minute precipitation dataset that covers the period from1951 to present.Preliminary evaluation reveals that the station density is high and the data continuity is good in most areas of China.However,the integrity of stations in some areas of western China is relatively poor.The availability rate and accuracy rate in summer are higher than 99%at most stations,with the overall availability and accuracy rates reaching as much as 99.42%and 99.22%,respectively.展开更多
基金supported by National Institutes of Health Grant DK083350 to M. W
文摘Lipoprotein receptor-related protein 6(LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells(MSCs), skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin1MSCs by crossing nestin-Cre mice with LRP6floxmice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin1cells demonstrated reductions in body weight and body length at 1 and 3 months of age. Bone architecture measured by microCT(mCT) showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix1osteoprogenitors and osteocalcin1osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.
文摘Bone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function.Recently,an increasing number of studies have characterized the significance of bone as an endocrine organ,suggesting that bone-derived factors regulate local bone metabolism and metabolic functions.In addition,these factors can regulate global energy homeostasis by altering insulin sensitivity,feeding behavior,and adipocyte commitment.These findings may provide a new pathological mechanism for related metabolic diseases or be used in the diagnosis,treatment,and prevention of metabolic diseases such as osteoporosis,obesity,and diabetes mellitus.In this review,we summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.
基金This study was supported by the Natural Science Foundation of Guangdong Province,China(2019A1515011614 to ZC)the Science and Technology Program of Guangzhou(202002030483 to ZC)+2 种基金the National Natural Science Foundation of China(81601942 to ZC and 81830079 to BY)the Outstanding Youths Development Scheme of Southern Medical University(2021YQPY008 to ZC)the National Key R&D Program of China(2019YFA0111900 to CL).
文摘The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration.We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA.However,the mechanism responsible for the elevation of H-type vessels in OA is still unclear.Here,we found that PDGFR-βexpression,predominantly in the CD31^(hi)Emcn^(hi) endothelium,was substantially elevated in subchondral bones from OA patients and rodent OA models.A mouse model of OA with deletion of PDGFR-βin endothelial cells(ECs)exhibited fewer H-type vessels,ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration.Endothelial PDGFR-βpromotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex.Notably,endothelium-specific inhibition of PDGFR-βby local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls.Based on the results from this study,targeting PDGFR-βis a novel and promising approach for the prevention or early treatment of OA.
基金supported by the National Institutes of Health grant DK083350the American Heart Association#15GRNT25280000
文摘Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids(oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation. We found that cell surface LRP6 in bone marrow mesenchymal stromal cells(MSCs) decreased rapidly in response to increased oxPLs in marrow microenvironment. LRP6 directly bound and mediated the uptake of oxPLs by MSCs. oxPL-LRP6 binding induced LRP6 endocytosis through a clathrin-mediated pathway, decreasing responses of MSCs to osteogenic factors and diminishing osteoblast differentiation ability. Thus, LRP6 functions as a receptor and molecular target of oxPLs for their adverse effect on MSCs, revealing a potential mechanism underlying atherosclerosis-associated bone loss.
基金supported by the Joint Funds of the National Natural Science Foundation of China (U1138303)
文摘How common reed(Phragmites australis Trin. ex Steud.) colonization correlates to soil heterogeneity and environmental determinants remains unclear in arid areas. We conducted a field investigation and soil sampling in 100 plots along Keriya River Basin to uncover the relationship between common reed and heterogeneous soils. Reed colonization variables and its soil properties were measured and recorded for the analysis of their relationship using Pearson correlation and redundancy analysis methods. The comparison results of common reed characteristics among 100 plots showed that common reeds performed strong tolerance and ecophysiological plasticity to edaphic stresses. Common reed colonization was tightly connected to soil heterogeneity according to the correlation analysis between its colonization characteristics and soil properties. Common reed colonization got feedbacks on soil properties as well, including the increase of soil organic matter and the alleviation of salt uplifting. The main limiting environmental determinant of common reed colonization was soil salt, followed by pH and soil water content.
基金supported by the National Natural Science Foundation of China(81930071,82072502)the National Natural Science Foundation Regional Innovation and Development Joint Fund(U21A20352)+5 种基金the National Key Research and Development Project(2022YFC3601900,2022YFC2505500)the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital,2021LNJJ06,2022LNJJ07)the Natural Science Foundation of Hunan Province(2022JJ20100)the Key Research and Development Program of Hunan Province(2021SK2017)the Science and Technology Innovation Program of Hunan Province(2022RC3075)the Central South University Innovation-Driven Research Program(2023CXQD031)。
文摘Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.
基金the National Natural Science Foundation of China(Nos.U1905217,52090034,and 51773008)the Fundamental Research Funds for the Central Universities(No.XK1802)is gratefully acknowledged.
文摘Although solar steam generation is an eco-friendly approach for desalinating seawater and purifying wastewater,there are still issues on how to improve the efficiency of solar energy utilization and accelerate the water and heat transport inside the solardriven water evaporators.Herein,we design a central hollow cylindrical reduced graphene oxide(RGO)foam with vertically and radially orientated channels as a solar steam generation device for efficient water evaporation and purification.The vertically aligned porous channels accelerate upward transport of water to the top evaporation surface,while the radially aligned porous channels facilitate water transport and heat transfer along the radial directions for fully utilizing the heat accumulated inside the central cylindrical hole of the foam.The central hole of the foam plays a highly positive role in accumulating more heat for accelerating the water evaporation,the newly generated inner sidewall resulted from the central hole can gain extra thermal energy from surrounding environment in the same way as the outer sidewall of the foam due to the surface cooling effect of the water evaporation.As a result,the vertically and radially aligned RGO foam evaporator with central hollow cylinder achieves a high solar steam generation rate of 2.32 kg·m^(−2)·h^(−1)with an exceptional energy conversion efficiency of 120.9%under 1-sun irradiation,superior to the vertically aligned RGO foam without the central hole(1.83 kg·m^(−2)·h^(−1),96.9%)because of the enhanced water and heat transfer inside the porous channels,the efficient utilization of environmental energy.
基金supported by National Natural Science Foundation of China(Nos.12022511,11861131010 and 12075279)the National Key Research and Development Program of China(Nos.2017YFE0301300 and 2017YFA0402500)+1 种基金the CASHIPS Director’s Fund(No.BJPY2019B01)the Key Research Program of Frontier Sciences of CAS(No.ZDBS-LY-SLH010).
文摘Dust presented in experimental advanced superconducting tokamak(EAST)with mixed plasmafacing materials has been collected and characterized for the first time.Dust at different positions in the vessel was collected by vacuum cleaner after the first experimental campaign in 2019.The shape,composition,and size of dust particles have been analyzed using different methods.About 80%of the total number of dust particles have size between 20 and 80μm,and most of dust particles are spherical,while schistose shape,columnar and irregular shape were also found.With the help of energy-dispersive x-ray spectroscopy different elements of dust have been identified,which is generally consistent with the different plasma-facing components in EAST.Both x-ray fluorescence and inductively coupled plasma emission spectrometer are complementary methods for measuring the dust composition quantitatively.It was found that the major components of dust were lithium dust in the form of lithium carbonate and lithium hydroxide,which is due to the routine lithium wall conditioning during EAST operation.
文摘In this paper, we prove a result on the uniqueness of meromorphic functions sharing three values counting multiplicity and improve a result obtained by Xiaomin Li and Hongxun Yi.
文摘With the increase of wind power capacity in China, the situation of curtailment of wind power is getting worse. An annual sequence production simulation model is established with maximum wind power consumption as the objective function. The calculation of specific power grid operation in 2013 verifies the precision of this model. The impact of different factors on wind power accommodation as well as the impact of power grid reserve, wind resources and load on wind power curtailment is analyzed. The calculation results quantify the impact of different factors from power system to the accommodation of wind power and provide reference to solving the problem of wind power curtailment.
基金Supported by the National Key Research and Development Program of China(2016YFA0600301 and 2016YFA0600302).
文摘The establishment of self-recording precipitation observation systems in China began in 1951,and strips of self-recording precipitation graph paper have been archived since then.More than 9 million sheets of self-recording graph paper from 2253 stations in 31 provinces have been digitized by using image scanning and curve extraction technology.Format specification and quality control have been applied to the digitized data,and the China Surface Self-Recording Per-Minute Precipitation Dataset(V1.0)has been developed.The integrity and accuracy of this dataset are evaluated.This is the first attempt in China to establish a per-minute precipitation dataset that covers the period from1951 to present.Preliminary evaluation reveals that the station density is high and the data continuity is good in most areas of China.However,the integrity of stations in some areas of western China is relatively poor.The availability rate and accuracy rate in summer are higher than 99%at most stations,with the overall availability and accuracy rates reaching as much as 99.42%and 99.22%,respectively.
