Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a s...Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.展开更多
Biodegradable magnesium(Mg)and its alloys exhibit excellent biocompatibility and mechanical compatibility,demonstrating tremendous potential for applications in orthopedics.However,the rapid degradation rate has limit...Biodegradable magnesium(Mg)and its alloys exhibit excellent biocompatibility and mechanical compatibility,demonstrating tremendous potential for applications in orthopedics.However,the rapid degradation rate has limited their clinical application.Polycaprolactone(PCL)is commonly employed as a polymer coating to impede the rapid degradation of Mg.Unfortunately,its long-term anti-corrosion capability and bioactivity are inadequate.To address these issues,polydopamine(PDA)-modified zeolitic imidazolate framework-8(PZIF-8)bioactive nanoparticles are fabricated and incorporated into the PCL coating.The PZIF-8 particles,featuring catechol motifs,can enhance the compactness of the PCL coating,reduce its defects,and possess biomineralization ability,thereby effectively improving its anti-corrosive and bioactive properties.Moreover,the active substances released from the degradation of the PZIF-8 particles such as Zn^(2+)and PDA are beneficial for osteogenesis.The corrosion tests indicate that the corrosion current density of PCL-treated sample decreases by more than one order of magnitude and the amount of H_(2)released decreases from 0.23±0.12 to 0.08±0.08 ml cm^(-2)after doping with the PZIF-8.Furthermore,the improved corrosion resistance and released PDA and Zn^(2+)from the coating can promote osteogenic differentiation by up-regulating the expression of alkaline phosphatase activity,related osteogenic genes,and proteins.In addition,in vivo implantation experiments in rabbit femur defects further offer strong evidence that the doping of PZIF-8 nanoparticles accelerates bone reconstruction of the PCL coating.In summary,this work implies a new strategy to fabricate a PCL-based coating on Mg-based implants by introducing the PZIF-8 particles for orthopedic applications.展开更多
This paper proposes a multi-criteria decision-making (MCGDM) method based on the improved single-valued neutrosophic Hamacher weighted averaging (ISNHWA) operator and grey relational analysis (GRA) to overcome the lim...This paper proposes a multi-criteria decision-making (MCGDM) method based on the improved single-valued neutrosophic Hamacher weighted averaging (ISNHWA) operator and grey relational analysis (GRA) to overcome the limitations of present methods based on aggregation operators. First, the limitations of several existing single-valued neutrosophic weighted averaging aggregation operators (i.e. , the single-valued neutrosophic weighted averaging, single-valued neutrosophic weighted algebraic averaging, single-valued neutrosophic weighted Einstein averaging, single-valued neutrosophic Frank weighted averaging, and single-valued neutrosophic Hamacher weighted averaging operators), which can produce some indeterminate terms in the aggregation process, are discussed. Second, an ISNHWA operator was developed to overcome the limitations of existing operators. Third, the properties of the proposed operator, including idempotency, boundedness, monotonicity, and commutativity, were analyzed. Application examples confirmed that the ISNHWA operator and the proposed MCGDM method are rational and effective. The proposed improved ISNHWA operator and MCGDM method can overcome the indeterminate results in some special cases in existing single-valued neutrosophic weighted averaging aggregation operators and MCGDM methods.展开更多
Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors,...Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.展开更多
Additive manufacturing(AM)of Mg alloys has become a promising strategy for producing complex structures,but the corrosion performance of AM Mg components remains unexploited.In this study,wire and arc additive manufac...Additive manufacturing(AM)of Mg alloys has become a promising strategy for producing complex structures,but the corrosion performance of AM Mg components remains unexploited.In this study,wire and arc additive manufacturing(WAAM)was employed to produce single AZ31 layer.The results revealed that the WAAM AZ31 was characterized by significant grain refinement with non-textured crystallographic orientation,similar phase composition and stabilized corrosion performance comparing to the cast AZ31.These varied corrosion behaviors were principally ascribed to the size of grain,where cast AZ31 and WAAM AZ31 were featured by micro galvanic corrosion and intergranular corrosion,respectively.展开更多
Axinl is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined.In the present studies,we determined changes in postnatal bone growth by deletion of Axinl in osteobla...Axinl is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined.In the present studies,we determined changes in postnatal bone growth by deletion of Axinl in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1 O5X mice and found that hypertrophic cartilage area was largely expanded in AxinlOSX KO mice.A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1OSX KO mice.Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased,demonstrated by decreased TRAPpositive cell numbers,associated with reduction of MMP9-and cathepsin K-positive cell numbers in Axin1 O5X KO mice.OPG expression and the ratio of O p g to Rankl were significantly increased in osteoblasts of Axinl O5X KO mice.Osteoclast formation in primary bone marrow derived microphage(BMM)cells was significantly decreased when BMM cells were cultured with conditioned media(CM)collected from osteoblasts derived from Axin1OSX mice compared with BMM cells cultured with CM derived from WT mice.Thus,the loss of Axinl in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation,leading to delayed bone growth in postnatal Axin1°sx KO mice.展开更多
Dear Editor,Transposable phages,which are reproduced by transposition(Harshey,2012;Taylor,1963),have been widely applied in the field of biotechnology to manipulate operon/gene fusions,in vivo cloning,randomion mutage...Dear Editor,Transposable phages,which are reproduced by transposition(Harshey,2012;Taylor,1963),have been widely applied in the field of biotechnology to manipulate operon/gene fusions,in vivo cloning,randomion mutagenesis,and integration of DNA into bacterial genomes(Abalakina et al.,2008;Akhverdyan et al.,2011).One of the best-studied transposable phages is展开更多
Thermally grown oxide(TGO)is a critical factor for the service life of thermal barrier coatings(TBC).Numerical simulations of the growth process of TGO have become an effective means of comprehensively understanding t...Thermally grown oxide(TGO)is a critical factor for the service life of thermal barrier coatings(TBC).Numerical simulations of the growth process of TGO have become an effective means of comprehensively understanding the progressive damage of the TBC system.At present,technologies of numerical simulation to TGO growth include two categories:coupled chemical-mechanical methods and mechanical equivalent methods.The former is based on the diffusion analysis of oxidizing elements,which can describe the influence of bond coat(BC)consumption and phase transformation in the growth process of TGO on the mechanical behavior of each layer of TBC,and has high accuracy for the thickness evolution of TGO,but they cannot describe the lateral growth of TGO and the rumpling phenomenon induced.The latter focuses on describing the final stress and strain state after the growth of a specific TGO rather than the complete growth processes of TGO.Based on the measured TGO thickness growth curve,simulations of thickening and lateral growth can be achieved by directly applying anisotropic volumetric strain to oxidized elements and switching elements properties from the BC to the TGO.展开更多
When the plant-mixed thermal regeneration technology is adopted for the waste asphalt pavement mixtures,its performance can basically reach the level of freshly-mixed asphalt concrete,which can be used for paving the ...When the plant-mixed thermal regeneration technology is adopted for the waste asphalt pavement mixtures,its performance can basically reach the level of freshly-mixed asphalt concrete,which can be used for paving the middle and lower layers of road pavements of various grades.Through the research and application of plant-mixed thermal regeneration technology based on China's Kunming-Yuxi Expressway Pavement Overhaul Project,this paper summarizes relevant technical points and effectively advocates the promotion and application of this technology in highway maintenance.展开更多
Sodium salts of mono-and di-carboxylic acids(glycolic,fumaric and benzoic acid)were studied as corrosion inhibitors for AM50 alloy in pH neutral aqueous NaCl environment.Hydrogen evolution,electrochemical and surface ...Sodium salts of mono-and di-carboxylic acids(glycolic,fumaric and benzoic acid)were studied as corrosion inhibitors for AM50 alloy in pH neutral aqueous NaCl environment.Hydrogen evolution,electrochemical and surface characterization techniques were employed to reveal their corrosion inhibition mechanism,whilst the molecular features of inhibitors were investigated by quantum chemical calculation.All inhibitors reduced anodic dissolution of AM50 and their efficiency generally increased with time and concentration from 5 mM to 100 mM.The inhibition mechanism can be described as physisorption of inhibitive molecules on the surface of the intrinsic oxide layer followed by chemisorption with Mg^(2+)and Al^(3+),and the difference in inhibition action among these inhibitors was explained on the molecular scale.展开更多
Magnesium(Mg)alloys are attractive biodegradable implant materials.The degradation products on Mg alloys play a critical role in the stability of the interface between implant and surrounding tissue.In the present stu...Magnesium(Mg)alloys are attractive biodegradable implant materials.The degradation products on Mg alloys play a critical role in the stability of the interface between implant and surrounding tissue.In the present study,the effects of dynamic deformation on the interface layer of biomedical Mg-1Zn alloy were investigated using the constant extension rate tensile tests(CERT)coupled with electrochemical impedance spectroscopy(EIS).The deformation of the Mg-1Zn alloy had an adverse influence on the impedance of the surface degradation layer formed in simulated body fluid that only containing inorganic compounds.However,the surface degradation layer with improved corrosion resistance was obtained for the strained samples tested in protein-containing simulated body fluid.The spontaneous or enhanced adsorption of protein into the degradation product led to a flexible and stable hybrid anti-corrosive layer.A relationship between the dynamic deformation of Mg alloy and the impendence of the degradation layer was established,which demonstrates the necessity for in situ characterisation of the evolution of the surface layer under dynamic condition.展开更多
Stress-induced cardiomyopathy,in contrast to acute myocardial infarction,is a type of acute heart failure characterized by reversible left ventricular dysfunction.Cardiac imaging primarily reveals left ventricle myoca...Stress-induced cardiomyopathy,in contrast to acute myocardial infarction,is a type of acute heart failure characterized by reversible left ventricular dysfunction.Cardiac imaging primarily reveals left ventricle myocardial stunning,81.7%of which is apical type.Emotional or psychological stress usually precedes the onset of stress-induced cardiomyopathy,which is increasingly being recognized as a unique neurogenic myocardial stunning disease.To distinguish between acute myocardial infarction and acute viral or auto-immune myocarditis,this review summarizes specific mechanisms of myocardial stunning in stress-induced cardiomyopathy,such as calcium disorders,metabolic alterations,anatomical and histological variations in different parts of the left ventricle,and microvascular dysfunction.展开更多
Cryptomeria fortunei(Chinese cedar)is a highly adaptable woody species and one of the main forest plantation trees in subtropical high-altitude areas in China.However,there are few studies on its chloroplast(cp)genome...Cryptomeria fortunei(Chinese cedar)is a highly adaptable woody species and one of the main forest plantation trees in subtropical high-altitude areas in China.However,there are few studies on its chloroplast(cp)genome.In this study,the complete cp genome of C.fortunei was sequenced and evaluated via comparative analyses with those of related species(formerly the Taxodiaceae)in Cupressaceae.The C.fortunei cp genome was 131,580 bp in length,and the GC content of the whole genome was 35.38%.It lost one relevant large inverted repeat and contained 114 unique genes,including 82 protein-coding genes,28 tRNAs and 4 rRNAs.The relative synonymous codon usage(RSCU)of codons ending with A/U was more than twice that of codons ending with G/C.Thirty long repeat structures(LRSs)and 213 simple sequence repeat(SSR)loci were detected in the C.fortunei cp genome.Comparative analyses of 10 cp genomes revealed that substantial rearrangements occurred in the gene organization.Additionally,6 cp hotspot regions(trnS-GGA,ycf1,trnP-GGG,trnC-GCA,psbZ and accD)were identified,and 4 genes(petL,psbM,rpl22 and psaM)had likely underwent positive selection.Phylogenetic analysis showed that Cupressaceae,Taxaceae and Cephalotaxaceae clustered to form a clade and that C.fortunei was most closely related to C.japonica(Japanese cedar),C.japonica cv.Wogon Hort and Taxodium distichum(baldcypress).These results provide references for future studies of population genetics,phylogenetic status and molecular markers among Cupressaceae species and for the cultivation of improved varieties.展开更多
The population size class structure, survival curve, height class structure and population distribution patterns of Ilex cornuta in Longgan Lake National Nature Preserve, Hubei Province, were investigated by using the...The population size class structure, survival curve, height class structure and population distribution patterns of Ilex cornuta in Longgan Lake National Nature Preserve, Hubei Province, were investigated by using the adjacent grid method. The result showed that the population age structure of I. cornuta was of middle-aging type, in the vertical space of population individuals, most of them lived in the shrub layer, and a small number of individuals entered the arborous layer. The distribution pattern of I. cornuta was analyzed by variance /mean ratio method, and the results showed that the distribution pattern of the population was the cluster type. This study can provide references for the further protection, research and development and utilization of I. cornuta .展开更多
Along with the popularization and application of the steel bridge in China,due to the high modulus of asphalt concrete with good waterproof,anti-fatigue,anti-aging and good performance,asphalt concrete with high modul...Along with the popularization and application of the steel bridge in China,due to the high modulus of asphalt concrete with good waterproof,anti-fatigue,anti-aging and good performance,asphalt concrete with high modulus was widely used in steel bridge deck pavement,the test and comparative study of high modulus asphalt concrete were carried out based on two types of common high modulus asphalt concrete which include the casting type asphalt concrete and epoxy resin modified asphalt concrete,aims to further explore the performance features of the steel bridge deck with high modulus asphalt concrete,and provide help on the application of this asphalt concrete on the steel bridge deck.展开更多
This paper aims to tackle the calculation efficiency problem raised in the cavitation-flow simulation of the aviation centrifugal pump due to the fading-away interface resulting from the dissipation of numerics used i...This paper aims to tackle the calculation efficiency problem raised in the cavitation-flow simulation of the aviation centrifugal pump due to the fading-away interface resulting from the dissipation of numerics used in the phase-change control equation for unstructured-grid multiphase flow,and due to the limitation of flow time-step in whole flow regimes,the control equation of vapor–liquid two-phase flow considering cavitation mass transport is established firstly,modifying the momentum equation by introducing the surface tension,and adding the artificial convective flow to the phase equation to solve the numerical dissipation problem.Secondly,in consideration of the local time step principle and based on the multi-dimensional general limiter algorithm with explicit solutions under the OpenFOAM platform,a solution method of steady-state VOF (Volume of Fluid) model considering cavitation two-phase change is constructed,and the feasibility of this method is verified by NACA hydrofoil and NASA flat plate inducer.Finally,based on the platform developed,the cavitation performance of an aviation centrifugal pump inducer is analyzed.The research results show that the error of the calculated cavitation pressure distribution for NACA hydrofoil between the simulation test and the experimental-test is less than 5%,and the maximum error of calculated cavitation number at pump head dropping for NASA high-speed flat plate inducer between the simulation test and the experimental-test is 2.1%.The cavitation area observed in the simulation test is the same as that obtained in the high-speed photography test.Based on the OpenFOAM simulation method,the position of pump head dropping of the fuel centrifugal pump can be accurately captured.The error of the calculated cavitation number at pump head dropping between the simulation test and the experimental test is about 3.7%,showing high calculation accuracy.展开更多
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
基金financially supported by the Guangzhou Science and Technology Project(Nos.2021A0505030042 and 201904010060)Guangdong Basic and Applied Basic Research Foundation(No.2020B1515120078)+2 种基金National Natural Science Foundation of China(Nos.81401766 and 32101059)Natural Science Foundation of Guangdong Province(No.2022A1515010266)Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration and Shenzhen People’s Hospital(No.ZDSYS20200811143752005)。
文摘Biodegradable magnesium(Mg)and its alloys exhibit excellent biocompatibility and mechanical compatibility,demonstrating tremendous potential for applications in orthopedics.However,the rapid degradation rate has limited their clinical application.Polycaprolactone(PCL)is commonly employed as a polymer coating to impede the rapid degradation of Mg.Unfortunately,its long-term anti-corrosion capability and bioactivity are inadequate.To address these issues,polydopamine(PDA)-modified zeolitic imidazolate framework-8(PZIF-8)bioactive nanoparticles are fabricated and incorporated into the PCL coating.The PZIF-8 particles,featuring catechol motifs,can enhance the compactness of the PCL coating,reduce its defects,and possess biomineralization ability,thereby effectively improving its anti-corrosive and bioactive properties.Moreover,the active substances released from the degradation of the PZIF-8 particles such as Zn^(2+)and PDA are beneficial for osteogenesis.The corrosion tests indicate that the corrosion current density of PCL-treated sample decreases by more than one order of magnitude and the amount of H_(2)released decreases from 0.23±0.12 to 0.08±0.08 ml cm^(-2)after doping with the PZIF-8.Furthermore,the improved corrosion resistance and released PDA and Zn^(2+)from the coating can promote osteogenic differentiation by up-regulating the expression of alkaline phosphatase activity,related osteogenic genes,and proteins.In addition,in vivo implantation experiments in rabbit femur defects further offer strong evidence that the doping of PZIF-8 nanoparticles accelerates bone reconstruction of the PCL coating.In summary,this work implies a new strategy to fabricate a PCL-based coating on Mg-based implants by introducing the PZIF-8 particles for orthopedic applications.
文摘This paper proposes a multi-criteria decision-making (MCGDM) method based on the improved single-valued neutrosophic Hamacher weighted averaging (ISNHWA) operator and grey relational analysis (GRA) to overcome the limitations of present methods based on aggregation operators. First, the limitations of several existing single-valued neutrosophic weighted averaging aggregation operators (i.e. , the single-valued neutrosophic weighted averaging, single-valued neutrosophic weighted algebraic averaging, single-valued neutrosophic weighted Einstein averaging, single-valued neutrosophic Frank weighted averaging, and single-valued neutrosophic Hamacher weighted averaging operators), which can produce some indeterminate terms in the aggregation process, are discussed. Second, an ISNHWA operator was developed to overcome the limitations of existing operators. Third, the properties of the proposed operator, including idempotency, boundedness, monotonicity, and commutativity, were analyzed. Application examples confirmed that the ISNHWA operator and the proposed MCGDM method are rational and effective. The proposed improved ISNHWA operator and MCGDM method can overcome the indeterminate results in some special cases in existing single-valued neutrosophic weighted averaging aggregation operators and MCGDM methods.
基金supported by grants from the National Key Research and Development Program of China (2020YFC2002800 to J.L. and 2018YFC1105102 to J.L.)the National Natural Science Foundation of China (91949127, 92168204 to J.L.)the Fundamental Research Funds for the Central Universities (22120210586)
文摘Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.
基金the financial support by National Key Research and Development Project(Grand No.2020YFC1107202)Guangdong Basic and Applied Basic Research Foundation(Grand No.2020A1515110754)+3 种基金MOE Key Lab of Disaster Forest and Control in Engineering,Jinan University(Grand No.20200904008)Educational Commission of Guangdong Province(Grand No.2020KTSCX012)the Fundamental Research Funds for Central Universities(Grand No.21620342)the support from National Natural Science Foundation of China,NSFC(Grand No.51775556)。
文摘Additive manufacturing(AM)of Mg alloys has become a promising strategy for producing complex structures,but the corrosion performance of AM Mg components remains unexploited.In this study,wire and arc additive manufacturing(WAAM)was employed to produce single AZ31 layer.The results revealed that the WAAM AZ31 was characterized by significant grain refinement with non-textured crystallographic orientation,similar phase composition and stabilized corrosion performance comparing to the cast AZ31.These varied corrosion behaviors were principally ascribed to the size of grain,where cast AZ31 and WAAM AZ31 were featured by micro galvanic corrosion and intergranular corrosion,respectively.
基金National Natural Science Foundation of China(NSFC)(81973876,81673991 to BS,81730107 to YJW and 81603643 to YJZ)The National Key R&D Program of China(2018YFC1704302 to YJW)+3 种基金The Program for Innovative Research Team in University,Ministry of Education of China(IRT1270 to YJW)The Program for Innovative Research Team,Ministry of Science and Technology of China(2015RA4002 to YJW)The Three Years Action to Accelerate the Development of Traditional Chinese Medicine Plan(ZY(2018-2020)-CCCX-3003 to YJW)National Natural Science Foundation of China(NSFC)(81672227)and a Frontier Science of CAS grant(QYZDB-SSW-JSC030)to HP.National Natural Science Foundation of China(NSFC)(81991513)to GX.
文摘Axinl is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined.In the present studies,we determined changes in postnatal bone growth by deletion of Axinl in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1 O5X mice and found that hypertrophic cartilage area was largely expanded in AxinlOSX KO mice.A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1OSX KO mice.Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased,demonstrated by decreased TRAPpositive cell numbers,associated with reduction of MMP9-and cathepsin K-positive cell numbers in Axin1 O5X KO mice.OPG expression and the ratio of O p g to Rankl were significantly increased in osteoblasts of Axinl O5X KO mice.Osteoclast formation in primary bone marrow derived microphage(BMM)cells was significantly decreased when BMM cells were cultured with conditioned media(CM)collected from osteoblasts derived from Axin1OSX mice compared with BMM cells cultured with CM derived from WT mice.Thus,the loss of Axinl in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation,leading to delayed bone growth in postnatal Axin1°sx KO mice.
基金supported by the National Basic Research Program(973 Program)of China(2014CB745100)the National Key Technologies R&D Program of China(2012AA022101)
文摘Dear Editor,Transposable phages,which are reproduced by transposition(Harshey,2012;Taylor,1963),have been widely applied in the field of biotechnology to manipulate operon/gene fusions,in vivo cloning,randomion mutagenesis,and integration of DNA into bacterial genomes(Abalakina et al.,2008;Akhverdyan et al.,2011).One of the best-studied transposable phages is
基金supported by the National Natural Science Foundation of China(61202369)the NSFC-Zhejiang Joint Fund for the Integration of Industrialization and Informatization(U1509219)
基金supported by the National Natural Science Foundation of China(Grant No.51905510)National Science and Technology Major Project(J2019-IV-0003-0070).
文摘Thermally grown oxide(TGO)is a critical factor for the service life of thermal barrier coatings(TBC).Numerical simulations of the growth process of TGO have become an effective means of comprehensively understanding the progressive damage of the TBC system.At present,technologies of numerical simulation to TGO growth include two categories:coupled chemical-mechanical methods and mechanical equivalent methods.The former is based on the diffusion analysis of oxidizing elements,which can describe the influence of bond coat(BC)consumption and phase transformation in the growth process of TGO on the mechanical behavior of each layer of TBC,and has high accuracy for the thickness evolution of TGO,but they cannot describe the lateral growth of TGO and the rumpling phenomenon induced.The latter focuses on describing the final stress and strain state after the growth of a specific TGO rather than the complete growth processes of TGO.Based on the measured TGO thickness growth curve,simulations of thickening and lateral growth can be achieved by directly applying anisotropic volumetric strain to oxidized elements and switching elements properties from the BC to the TGO.
文摘When the plant-mixed thermal regeneration technology is adopted for the waste asphalt pavement mixtures,its performance can basically reach the level of freshly-mixed asphalt concrete,which can be used for paving the middle and lower layers of road pavements of various grades.Through the research and application of plant-mixed thermal regeneration technology based on China's Kunming-Yuxi Expressway Pavement Overhaul Project,this paper summarizes relevant technical points and effectively advocates the promotion and application of this technology in highway maintenance.
基金the financial support by Guangdong Basic and Applied Basic Research Founding (Grand No. 2020A1515110754)MOE Key Lab of Disaster Forest and Control in Engineering, Jinan University (Grand No. 20200904008)+4 种基金Educational Commission of Guangdong Province (Grand No. 2020KTSCX012)the Fundamental Research Funds for Central Universities (Grand No. 21620342)the High Performance Public Computing Service Platform of Jinan Universitythe financial support from National Natural Science Foundation of China (Grand No. 52071067)the Fundamental Research Funds for the Central Universities (Grand No. N2002009)。
文摘Sodium salts of mono-and di-carboxylic acids(glycolic,fumaric and benzoic acid)were studied as corrosion inhibitors for AM50 alloy in pH neutral aqueous NaCl environment.Hydrogen evolution,electrochemical and surface characterization techniques were employed to reveal their corrosion inhibition mechanism,whilst the molecular features of inhibitors were investigated by quantum chemical calculation.All inhibitors reduced anodic dissolution of AM50 and their efficiency generally increased with time and concentration from 5 mM to 100 mM.The inhibition mechanism can be described as physisorption of inhibitive molecules on the surface of the intrinsic oxide layer followed by chemisorption with Mg^(2+)and Al^(3+),and the difference in inhibition action among these inhibitors was explained on the molecular scale.
基金supported by National Key R&D Program of China(2017YFB0305100,2017YFB0305104)the Science and Technology Planning Project of Guangdong Province No.2017B090903005+2 种基金the financial support from Jinan University(No.21620110)the financial support from Science and Technology Planning Project of Guangdong Province(No.2021A0505030042)the financial support from Guangdong Basic and Applied Basic Research Foundation(2019A1515110580)。
文摘Magnesium(Mg)alloys are attractive biodegradable implant materials.The degradation products on Mg alloys play a critical role in the stability of the interface between implant and surrounding tissue.In the present study,the effects of dynamic deformation on the interface layer of biomedical Mg-1Zn alloy were investigated using the constant extension rate tensile tests(CERT)coupled with electrochemical impedance spectroscopy(EIS).The deformation of the Mg-1Zn alloy had an adverse influence on the impedance of the surface degradation layer formed in simulated body fluid that only containing inorganic compounds.However,the surface degradation layer with improved corrosion resistance was obtained for the strained samples tested in protein-containing simulated body fluid.The spontaneous or enhanced adsorption of protein into the degradation product led to a flexible and stable hybrid anti-corrosive layer.A relationship between the dynamic deformation of Mg alloy and the impendence of the degradation layer was established,which demonstrates the necessity for in situ characterisation of the evolution of the surface layer under dynamic condition.
基金supported primarily by the Distinguished Young Foundations of the First Affiliated Hospital of Harbin Medical University(HYD2020JQ002 to Dr Yin)The Science Foundation of the First Affiliated Hospital of Harbin Medical University(2018 L001 to Dr Yin).
文摘Stress-induced cardiomyopathy,in contrast to acute myocardial infarction,is a type of acute heart failure characterized by reversible left ventricular dysfunction.Cardiac imaging primarily reveals left ventricle myocardial stunning,81.7%of which is apical type.Emotional or psychological stress usually precedes the onset of stress-induced cardiomyopathy,which is increasingly being recognized as a unique neurogenic myocardial stunning disease.To distinguish between acute myocardial infarction and acute viral or auto-immune myocarditis,this review summarizes specific mechanisms of myocardial stunning in stress-induced cardiomyopathy,such as calcium disorders,metabolic alterations,anatomical and histological variations in different parts of the left ventricle,and microvascular dysfunction.
基金This research was funded by the National Forestry and Grassland Administration of China,National Forestry Public Welfare Industry Research Project(Grant No.201304104)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Cryptomeria fortunei(Chinese cedar)is a highly adaptable woody species and one of the main forest plantation trees in subtropical high-altitude areas in China.However,there are few studies on its chloroplast(cp)genome.In this study,the complete cp genome of C.fortunei was sequenced and evaluated via comparative analyses with those of related species(formerly the Taxodiaceae)in Cupressaceae.The C.fortunei cp genome was 131,580 bp in length,and the GC content of the whole genome was 35.38%.It lost one relevant large inverted repeat and contained 114 unique genes,including 82 protein-coding genes,28 tRNAs and 4 rRNAs.The relative synonymous codon usage(RSCU)of codons ending with A/U was more than twice that of codons ending with G/C.Thirty long repeat structures(LRSs)and 213 simple sequence repeat(SSR)loci were detected in the C.fortunei cp genome.Comparative analyses of 10 cp genomes revealed that substantial rearrangements occurred in the gene organization.Additionally,6 cp hotspot regions(trnS-GGA,ycf1,trnP-GGG,trnC-GCA,psbZ and accD)were identified,and 4 genes(petL,psbM,rpl22 and psaM)had likely underwent positive selection.Phylogenetic analysis showed that Cupressaceae,Taxaceae and Cephalotaxaceae clustered to form a clade and that C.fortunei was most closely related to C.japonica(Japanese cedar),C.japonica cv.Wogon Hort and Taxodium distichum(baldcypress).These results provide references for future studies of population genetics,phylogenetic status and molecular markers among Cupressaceae species and for the cultivation of improved varieties.
基金Supported by the Team Project of Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains(2015TD06)
文摘The population size class structure, survival curve, height class structure and population distribution patterns of Ilex cornuta in Longgan Lake National Nature Preserve, Hubei Province, were investigated by using the adjacent grid method. The result showed that the population age structure of I. cornuta was of middle-aging type, in the vertical space of population individuals, most of them lived in the shrub layer, and a small number of individuals entered the arborous layer. The distribution pattern of I. cornuta was analyzed by variance /mean ratio method, and the results showed that the distribution pattern of the population was the cluster type. This study can provide references for the further protection, research and development and utilization of I. cornuta .
文摘Along with the popularization and application of the steel bridge in China,due to the high modulus of asphalt concrete with good waterproof,anti-fatigue,anti-aging and good performance,asphalt concrete with high modulus was widely used in steel bridge deck pavement,the test and comparative study of high modulus asphalt concrete were carried out based on two types of common high modulus asphalt concrete which include the casting type asphalt concrete and epoxy resin modified asphalt concrete,aims to further explore the performance features of the steel bridge deck with high modulus asphalt concrete,and provide help on the application of this asphalt concrete on the steel bridge deck.
基金supported by the National Science and Technology Major Project, China (No. J2019-V-0016-0111)the Aviation Engine and Gas Turbine Basic Science Center Project, China (No. P2022-B-V-003-001)+3 种基金the Defense Industrial Technology Development Program, China (No. JCKY2022607C002)the AECC Industry University Cooperation Project, China (No. HFZL2022CXY013)the National Natural Science Foundation of China (No. 52372396)the Key R&D Project in Shaanxi Province, China (No. 2021GXLH-01-16)。
文摘This paper aims to tackle the calculation efficiency problem raised in the cavitation-flow simulation of the aviation centrifugal pump due to the fading-away interface resulting from the dissipation of numerics used in the phase-change control equation for unstructured-grid multiphase flow,and due to the limitation of flow time-step in whole flow regimes,the control equation of vapor–liquid two-phase flow considering cavitation mass transport is established firstly,modifying the momentum equation by introducing the surface tension,and adding the artificial convective flow to the phase equation to solve the numerical dissipation problem.Secondly,in consideration of the local time step principle and based on the multi-dimensional general limiter algorithm with explicit solutions under the OpenFOAM platform,a solution method of steady-state VOF (Volume of Fluid) model considering cavitation two-phase change is constructed,and the feasibility of this method is verified by NACA hydrofoil and NASA flat plate inducer.Finally,based on the platform developed,the cavitation performance of an aviation centrifugal pump inducer is analyzed.The research results show that the error of the calculated cavitation pressure distribution for NACA hydrofoil between the simulation test and the experimental-test is less than 5%,and the maximum error of calculated cavitation number at pump head dropping for NASA high-speed flat plate inducer between the simulation test and the experimental-test is 2.1%.The cavitation area observed in the simulation test is the same as that obtained in the high-speed photography test.Based on the OpenFOAM simulation method,the position of pump head dropping of the fuel centrifugal pump can be accurately captured.The error of the calculated cavitation number at pump head dropping between the simulation test and the experimental test is about 3.7%,showing high calculation accuracy.