Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer ...Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.展开更多
In many practical structures, physical parameters of material and applied loads have random property.To optimize this kind of structures,an optimum mathematical model was built.This model has reliability constraints o...In many practical structures, physical parameters of material and applied loads have random property.To optimize this kind of structures,an optimum mathematical model was built.This model has reliability constraints on dynamic stress and displacement and upper & lower limits of the design variables. The numerical characteristic of dynamic response and sensitivity of dynamic response based on probability of structure were deduced respectively. By equivalent disposing, the reliability constraints were changed into conventional forms. The SUMT method was used in the optimization process.Two examples illustrate the correctness and practicability of the optimum model and solving approach.展开更多
BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD....BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.展开更多
While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and...While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases,and used it to study the effects of androgen deprivation in this microenvironment.The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds,leading to a mineralized osteoblast-derived microtissue containing,in a 3D setting,viable osteoblastic cells,osteocytic cells,and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins,and mineral content.Direct co-culture of androgen receptordependent/ independent cell lines (LNCaP,C4-2B,and PC3) led cancer cells to display functional and molecular features as observed in vivo.Co-cultured cancer cells showed increased affinity to the microtissues,as a function of their bone metastatic potential.Cocultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation,consistent with the clinical marker profile of osteoblastic bone metastases.LNCaP showed a significant adaptive response under androgen deprivation in the microtissues,with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase,enolase 2).Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor,alkaline phosphatase,and dopa decarboxylase,as seen in the transition towards resistance.The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.展开更多
This paper proposes a kind of least square modeling method based on typical signal response to enhance modeling accuracy of heat engineering process and adapts the environment that modeling experiment conditions are l...This paper proposes a kind of least square modeling method based on typical signal response to enhance modeling accuracy of heat engineering process and adapts the environment that modeling experiment conditions are limited. The principle of this method is, under the condition of known typical pulse, step and slope signal response and model structure, to give algorithm of model parameters of identified continuous system by least square mode through derivation. The method is applied to the identification of heat exchange process for a consumer substation, and identification result obtained is compared with that of other conventional methods. After the comparison the result shows that identification accuracy is improved obviously. In addition to the good identification accuracy, this method has the characteristics such as it can identify directly continuous system model, pure lagging time, and is not sensitive to data length in the identification process. All these characteristics show that this method is simple, easy to implement and has good practicability.展开更多
In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide...In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAAm-g-HA) has been synthesized as an injectable scaffold for cartilage tissue engineering. The aim of this study was to investigate the efficacy and cytocompatibility of PNIPAAm-g-HA to normal chondrocytes by using reverse transcription-polymerase chain reaction (RT-PCR) analysis and histochemical staining in preliminary in vitro and in vitro experiments. Hematoxylin and eosin staining showed homogeneous distribution of cells in the PNIPAAm-g-HA hydrogel in 3-dimensional in vitro cultivation. Alcian blue staining also indicated that abundant extracellular matrix formation, including acidic glycosaminoglycans, occurred in tissue-engineered cartilage over time in vitro. Cartilage-related gene expression patterns, which were tested in rabbit normal chondrocytes embedded in the hydrogel, were almost maintained for 4 weeks. Transforming growth factor-β1 (TGF-β1) stimulation enhanced the expression of SRY-related HMG box-containing gene 9 (Sox9) and type X collagen genes suggesting promotion of chondrogenic differentiation. Histochemical evaluation showed neocartilage formation following subcutaneous implantation of the chondrocyte-gel mixture in nude mice. Furthermore, TGF-β1 stimulation promoted production and maturation of the extracellular matrix of the in situ tissue engineered hyaline cartilage. These data suggested that PNIPAAm-g-HA could be a promising biomaterial, i.e., a self-assembling and injectable scaffold for cartilage tissue engineering.展开更多
Because of my carelessness,Eq.(1)in the paper "An approximate method for calculating the fluid force and response of a circular cylinder at lock-in"(China Ocean Engineering,22(3),2008,pp.373)should be f...Because of my carelessness,Eq.(1)in the paper "An approximate method for calculating the fluid force and response of a circular cylinder at lock-in"(China Ocean Engineering,22(3),2008,pp.373)should be f’-1.0/U’-5.0=f’;-1.0/5.75f’;-5.0,not f’=U’/5.75. My apology is hereby given.展开更多
Enhancement of nitrogen fixation in the rhizo-sphere of cereals has attracted a wide interestin biological and agricultural research,insteadof chemicals,for supplying higher plants withcombined nitrogen.Bacteria in as...Enhancement of nitrogen fixation in the rhizo-sphere of cereals has attracted a wide interestin biological and agricultural research,insteadof chemicals,for supplying higher plants withcombined nitrogen.Bacteria in association withrice plant.s were sensitive to the surroundingfactors in the soil,such as NH~+ or O,whichrepressed associative nitrogen fixation between展开更多
Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond th...Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.展开更多
The equivalent linearization method approximates the maximum displacement response of nonlinear structures through the corresponding equivalent linear system. By using the particle swarm optimization technique, a new ...The equivalent linearization method approximates the maximum displacement response of nonlinear structures through the corresponding equivalent linear system. By using the particle swarm optimization technique, a new statistical approach is developed to determine the key parameters of such an equivalent linear system over a 2D space of period and damping ratio. The new optimization criterion realizes the consideration of the structural safety margin in the equivalent linearization method when applied to the performance-based seismic design/evaluation of engineering structures. As an application, equations for equivalent system parameters of both bilinear hysteretic and stiffness degrading single-degree-of- freedom systems are deduced with the assumption of a constant ductility ratio. Error analyses are also performed to validate the proposed approach.展开更多
The Sichuan-Tibet transportation corridor is prone to numerous active faults and frequent strong earthquakes.While extensive studies have individually explored the effect of active faults and strong earthquakes on dif...The Sichuan-Tibet transportation corridor is prone to numerous active faults and frequent strong earthquakes.While extensive studies have individually explored the effect of active faults and strong earthquakes on different engineering structures,their combined effect remains unclear.This research employed multiple physical model tests to investigate the dynamic response of various engineering structures,including tunnels,bridges,and embankments,under the simultaneous influence of cumulative earthquakes and stick-slip misalignment of an active fault.The prototype selected for this study was the Kanding No.2 tunnel,which crosses the Yunongxi fault zone within the Sichuan-Tibet transportation corridor.The results demonstrated that the tunnel,bridge,and embankment exhibited amplification in response to the input seismic wave,with the amplification effect gradually decreasing as the input peak ground acceleration(PGA)increased.The PGAs of different engineering structures were weakened by the fault rupture zone.Nevertheless,the misalignment of the active fault may decrease the overall stiffness of the engineering structure,leading to more severe damage,with a small contribution from seismic vibration.Additionally,the seismic vibration effect might be enlarged with the height of the engineering structure,and the tunnel is supposed to have a smaller PGA and lower dynamic earth pressure compared to bridges and embankments in strong earthquake zones crossing active faults.The findings contribute valuable insights for evaluating the dynamic response of various engineering structures crossing an active fault and provide an experimental reference for secure engineering design in the challenging conditions of the Sichuan-Tibet transportation corridor.展开更多
Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells(MSC) to secrete brain-derived neurotrophic factor(BDNF) supports our plan to submit an Investigational N...Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells(MSC) to secrete brain-derived neurotrophic factor(BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease(HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis(ALS), spinocerebellar ataxia(SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine research.Notably,nanosecond pulsed electric fields(nsPEFs),characterized by short du...BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine research.Notably,nanosecond pulsed electric fields(nsPEFs),characterized by short duration and high strength,significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways.Consequently,we used transcriptomics to study changes in messenger RNA(mRNA),long noncoding RNA(lncRNA),microRNA(miRNA),and circular RNA expression during nsPEFs application.AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs.METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing.MSCs were pretreated with 5-pulse nsPEFs(100 ns at 10 kV/cm,1 Hz),followed by total RNA isolation.Each transcript was normalized by fragments per kilobase per million.Fold change and difference significance were applied to screen the differentially expressed genes(DEGs).Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions,complemented by quantitative polymerase chain reaction verification.RESULTS In total,263 DEGs were discovered,with 92 upregulated and 171 downregulated.DEGs were predominantly enriched in epithelial cell proliferation,osteoblast differentiation,mesenchymal cell differentiation,nuclear division,and wound healing.Regarding cellular components,DEGs are primarily involved in condensed chromosome,chromosomal region,actin cytoskeleton,and kinetochore.From aspect of molecular functions,DEGs are mainly involved in glycosaminoglycan binding,integrin binding,nuclear steroid receptor activity,cytoskeletal motor activity,and steroid binding.Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation.CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs,2 miRNAs,and 65 lncRNAs.Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways,which are involved in vesicular transport,calcium ion transport,cytoskeleton,and cell differentiation.展开更多
Novel poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-grafted hyaluronan [P(NIPAAm-co-NtBAAm)-g-HA] has been developed as a modified derivative to improve phase-transition characteristics of PNIPAAm-g-HA, which ...Novel poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-grafted hyaluronan [P(NIPAAm-co-NtBAAm)-g-HA] has been developed as a modified derivative to improve phase-transition characteristics of PNIPAAm-g-HA, which has a lower critical solution temperature (LCST) of approximately 32°C. This promising self-assembling biomaterial has potential as an injectable scaffold for in situ cartilage tissue engineering. LCST of the P(NIPAAm-co-NtBAAm)-g-HA decreased to approximately 3.6°C compared to that of the original PNIPAAm-g-HA. This modification enabled self-assembly at body temperatures lower than the temperature of the parental PNIPAAm-g-HA molecule. Cytotoxicity and acute systemic toxicity assays revealed that P(NIPAAm-co-NtBAAm)-g-HA was not hazardous. The DNA content of chondrogenic differentiated mesenchymal stem/stromal cells (MSCs) embedded in the gels was higher than that of biomaterial-free aggregates during the culture periods. Cartilage-related genes were also expressed in chondrogenic differentiated MSCs embedded in the P (NIPAAm-co-NtBAAm)-g-HA hydrogel. Specifically, an increased expression of SRY-related HMG box-containing gene 9 (Sox9) observed in the hydrogel group compared to controls. These data suggest that P(NIPAAm-co-NtBAAm)-g-HA is a promising injectable scaffold with thermoresponsive properties suitable for in situ cartilage tissue engineering.展开更多
The seismic damage to ancillary facilities on high-speed railway(HSR)bridges can affect the normal movement of trains.To propose the bridge deck acceleration response spectra of the typical HSR simply-supported girder...The seismic damage to ancillary facilities on high-speed railway(HSR)bridges can affect the normal movement of trains.To propose the bridge deck acceleration response spectra of the typical HSR simply-supported girder bridge for simplifying the seismic responses analysis of the facilities on bridges,the finite element models of the HSR multi-span simply-supported girder bridges with CRTSII track were established,and the numerical model was validated by tests.Besides,the effects of the span number,peak ground acceleration(PGA),pier height on the seismic acceleration and response spectra of the bridge deck were investigated.Afterward,the bridge acceleration amplification factor curves and bridge deck response spectra with different PGAs and pier heights were obtained.The formula for bridge deck acceleration amplification factor,with a 95%guarantee rate,was fitted.Moreover,the finite element models of the overhead contact lines(OCL)mounted on rigid base and bridges were established to validate the fitted formula.The results indicated that the maximum seismic acceleration response is in the midspan of the beam.The proposed formula for the bridge deck acceleration response spectra can be used to analyze the earthquake response of the OCL and other ancillary facilities on HSR simply-supported girder bridges.The bridge deck acceleration response spectra are conservative in terms of structural safety and can significantly improving the analysis efficiency.展开更多
In this paper,the current situation of agricultural environmental pollution caused by the increase of chemicals input in agriculture in China was analyzed,and it is found that agricultural pollution is related to agri...In this paper,the current situation of agricultural environmental pollution caused by the increase of chemicals input in agriculture in China was analyzed,and it is found that agricultural pollution is related to agricultural industrial policies,urban-rural economic structure,funds input in pollution control,comprehensive environmental management,laws of pollution control,and so forth. To control agricultural pollution effectively,it is needed to implement integration of agricultural and environmental policies,establish environmentally friendly agricultural technology popularizing system,implement integrated planning and management of a basin,and set up and improve legislation to protect agricultural environment.展开更多
Engine engineering database system is an oriented C AD applied database management system that has the capability managing distributed data. The paper discusses the security issue of the engine engineering database ma...Engine engineering database system is an oriented C AD applied database management system that has the capability managing distributed data. The paper discusses the security issue of the engine engineering database management system (EDBMS). Through studying and analyzing the database security, to draw a series of securi ty rules, which reach B1, level security standard. Which includes discretionary access control (DAC), mandatory access control (MAC) and audit. The EDBMS implem ents functions of DAC, MAC and multigranularity audit. DAC solves the problems o f role inheritance, right contain, authorization identify and cascade revoke, et c; MAC includes subject and object security setup rule, security modify rule and multilevel relation access operation rule, etc; Audit allows making the sub ject, object or operation type as different audit object to implement flexible a nd multigranularity audit method. The model is designed act as a security agent to access daemon database. At present, the model is implemented which runs on th e Windows 2000 environments.展开更多
基金National Natural Science Foundation of China under Grant No.51878508。
文摘Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.
文摘In many practical structures, physical parameters of material and applied loads have random property.To optimize this kind of structures,an optimum mathematical model was built.This model has reliability constraints on dynamic stress and displacement and upper & lower limits of the design variables. The numerical characteristic of dynamic response and sensitivity of dynamic response based on probability of structure were deduced respectively. By equivalent disposing, the reliability constraints were changed into conventional forms. The SUMT method was used in the optimization process.Two examples illustrate the correctness and practicability of the optimum model and solving approach.
文摘BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.
基金N.B.:IHBI ECR grant,Advance Queensland(AQ)Maternity Fund Award from the Queensland Government(DSITI),Young Researcher Award(2017-YR-RoW-9)from Lush(UK)supporting non-animal testing alternatives,National Health and Medical Research Council(NHMRC)Peter Doherty Early Career Research Fellowship(RF)(APP1091734)+5 种基金John Mills Young Investigator Award(YI0715)from the Prostate Cancer Foundation of Australia(PCFA)P.A.T.:Vice Chancellor’s RF(QUT)and AQ RF(QLD)J.A.C.:NHMRC PRFD.W.H.:Humboldt RF,ARC Industrial Transformation Training Center in Additive Biomanufacturing(IC160100026)NHMRC,World Cancer Foundation,National Breast Cancer Foundation,PCFA.D.W.H.,J.A.C.,C.C.N.:Movember Revolutionary Team Award(from Movember and PCFA).APCRC-Qthe Translational Research Institute are supported by grants from the Australian Government
文摘While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases,and used it to study the effects of androgen deprivation in this microenvironment.The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds,leading to a mineralized osteoblast-derived microtissue containing,in a 3D setting,viable osteoblastic cells,osteocytic cells,and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins,and mineral content.Direct co-culture of androgen receptordependent/ independent cell lines (LNCaP,C4-2B,and PC3) led cancer cells to display functional and molecular features as observed in vivo.Co-cultured cancer cells showed increased affinity to the microtissues,as a function of their bone metastatic potential.Cocultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation,consistent with the clinical marker profile of osteoblastic bone metastases.LNCaP showed a significant adaptive response under androgen deprivation in the microtissues,with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase,enolase 2).Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor,alkaline phosphatase,and dopa decarboxylase,as seen in the transition towards resistance.The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.
基金Sponsored by the National Eleventh Five-year Plan Key Project of Ministry of Science and Technology of China(Grant No.2006BAJ03A05)and SpecialFunds for Research of Scientific and Technological Innovation Talents in Harbin(Grant No.RC2006XK007001).
文摘This paper proposes a kind of least square modeling method based on typical signal response to enhance modeling accuracy of heat engineering process and adapts the environment that modeling experiment conditions are limited. The principle of this method is, under the condition of known typical pulse, step and slope signal response and model structure, to give algorithm of model parameters of identified continuous system by least square mode through derivation. The method is applied to the identification of heat exchange process for a consumer substation, and identification result obtained is compared with that of other conventional methods. After the comparison the result shows that identification accuracy is improved obviously. In addition to the good identification accuracy, this method has the characteristics such as it can identify directly continuous system model, pure lagging time, and is not sensitive to data length in the identification process. All these characteristics show that this method is simple, easy to implement and has good practicability.
文摘In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAAm-g-HA) has been synthesized as an injectable scaffold for cartilage tissue engineering. The aim of this study was to investigate the efficacy and cytocompatibility of PNIPAAm-g-HA to normal chondrocytes by using reverse transcription-polymerase chain reaction (RT-PCR) analysis and histochemical staining in preliminary in vitro and in vitro experiments. Hematoxylin and eosin staining showed homogeneous distribution of cells in the PNIPAAm-g-HA hydrogel in 3-dimensional in vitro cultivation. Alcian blue staining also indicated that abundant extracellular matrix formation, including acidic glycosaminoglycans, occurred in tissue-engineered cartilage over time in vitro. Cartilage-related gene expression patterns, which were tested in rabbit normal chondrocytes embedded in the hydrogel, were almost maintained for 4 weeks. Transforming growth factor-β1 (TGF-β1) stimulation enhanced the expression of SRY-related HMG box-containing gene 9 (Sox9) and type X collagen genes suggesting promotion of chondrogenic differentiation. Histochemical evaluation showed neocartilage formation following subcutaneous implantation of the chondrocyte-gel mixture in nude mice. Furthermore, TGF-β1 stimulation promoted production and maturation of the extracellular matrix of the in situ tissue engineered hyaline cartilage. These data suggested that PNIPAAm-g-HA could be a promising biomaterial, i.e., a self-assembling and injectable scaffold for cartilage tissue engineering.
文摘Because of my carelessness,Eq.(1)in the paper "An approximate method for calculating the fluid force and response of a circular cylinder at lock-in"(China Ocean Engineering,22(3),2008,pp.373)should be f’-1.0/U’-5.0=f’;-1.0/5.75f’;-5.0,not f’=U’/5.75. My apology is hereby given.
文摘Enhancement of nitrogen fixation in the rhizo-sphere of cereals has attracted a wide interestin biological and agricultural research,insteadof chemicals,for supplying higher plants withcombined nitrogen.Bacteria in association withrice plant.s were sensitive to the surroundingfactors in the soil,such as NH~+ or O,whichrepressed associative nitrogen fixation between
基金We acknowledge the funding support from the National Science Fund for Distinguished Young Scholars of National Natural Science Foundation of China(Grant No.42225702)the National Natural Science Foundation of China(Grant No.42077235).
文摘Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.
文摘The equivalent linearization method approximates the maximum displacement response of nonlinear structures through the corresponding equivalent linear system. By using the particle swarm optimization technique, a new statistical approach is developed to determine the key parameters of such an equivalent linear system over a 2D space of period and damping ratio. The new optimization criterion realizes the consideration of the structural safety margin in the equivalent linearization method when applied to the performance-based seismic design/evaluation of engineering structures. As an application, equations for equivalent system parameters of both bilinear hysteretic and stiffness degrading single-degree-of- freedom systems are deduced with the assumption of a constant ductility ratio. Error analyses are also performed to validate the proposed approach.
基金supported by the National Natural Science Foundation of China(Grant Nos.41825018,41977248,42207219)the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(Grant No.2019QZKK0904)。
文摘The Sichuan-Tibet transportation corridor is prone to numerous active faults and frequent strong earthquakes.While extensive studies have individually explored the effect of active faults and strong earthquakes on different engineering structures,their combined effect remains unclear.This research employed multiple physical model tests to investigate the dynamic response of various engineering structures,including tunnels,bridges,and embankments,under the simultaneous influence of cumulative earthquakes and stick-slip misalignment of an active fault.The prototype selected for this study was the Kanding No.2 tunnel,which crosses the Yunongxi fault zone within the Sichuan-Tibet transportation corridor.The results demonstrated that the tunnel,bridge,and embankment exhibited amplification in response to the input seismic wave,with the amplification effect gradually decreasing as the input peak ground acceleration(PGA)increased.The PGAs of different engineering structures were weakened by the fault rupture zone.Nevertheless,the misalignment of the active fault may decrease the overall stiffness of the engineering structure,leading to more severe damage,with a small contribution from seismic vibration.Additionally,the seismic vibration effect might be enlarged with the height of the engineering structure,and the tunnel is supposed to have a smaller PGA and lower dynamic earth pressure compared to bridges and embankments in strong earthquake zones crossing active faults.The findings contribute valuable insights for evaluating the dynamic response of various engineering structures crossing an active fault and provide an experimental reference for secure engineering design in the challenging conditions of the Sichuan-Tibet transportation corridor.
基金provided by a NIH NIGMS Predoctoral Fellowship T32GM099608(Deng)NIH NRSA Postdoctoral Fellowship F32NS090722(Fink)+2 种基金a NIH Director’s transformative award 1R01GM099688(Nolta)A Stewart’s and Dake Family Gift(Fink),California Institute for Regenerative Medicine(CIRM)DR2-05415(Wheelock/Nolta)philanthropic donors from the HD community,including the Roberson family and Team KJ
文摘Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells(MSC) to secrete brain-derived neurotrophic factor(BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease(HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis(ALS), spinocerebellar ataxia(SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.
基金Supported by the National Natural Science Foundation,China,No.82272568,81902247,and 32201013Natural Science Foundation of Shandong Province,China,No.ZR2021QH275+1 种基金Natural Science Foundation of Jinan City,China,No.202225070Guangdong Basic and Applied Basic Research Foundation,China,No.2022A1515220056.
文摘BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine research.Notably,nanosecond pulsed electric fields(nsPEFs),characterized by short duration and high strength,significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways.Consequently,we used transcriptomics to study changes in messenger RNA(mRNA),long noncoding RNA(lncRNA),microRNA(miRNA),and circular RNA expression during nsPEFs application.AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs.METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing.MSCs were pretreated with 5-pulse nsPEFs(100 ns at 10 kV/cm,1 Hz),followed by total RNA isolation.Each transcript was normalized by fragments per kilobase per million.Fold change and difference significance were applied to screen the differentially expressed genes(DEGs).Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions,complemented by quantitative polymerase chain reaction verification.RESULTS In total,263 DEGs were discovered,with 92 upregulated and 171 downregulated.DEGs were predominantly enriched in epithelial cell proliferation,osteoblast differentiation,mesenchymal cell differentiation,nuclear division,and wound healing.Regarding cellular components,DEGs are primarily involved in condensed chromosome,chromosomal region,actin cytoskeleton,and kinetochore.From aspect of molecular functions,DEGs are mainly involved in glycosaminoglycan binding,integrin binding,nuclear steroid receptor activity,cytoskeletal motor activity,and steroid binding.Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation.CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs,2 miRNAs,and 65 lncRNAs.Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways,which are involved in vesicular transport,calcium ion transport,cytoskeleton,and cell differentiation.
文摘Novel poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-grafted hyaluronan [P(NIPAAm-co-NtBAAm)-g-HA] has been developed as a modified derivative to improve phase-transition characteristics of PNIPAAm-g-HA, which has a lower critical solution temperature (LCST) of approximately 32°C. This promising self-assembling biomaterial has potential as an injectable scaffold for in situ cartilage tissue engineering. LCST of the P(NIPAAm-co-NtBAAm)-g-HA decreased to approximately 3.6°C compared to that of the original PNIPAAm-g-HA. This modification enabled self-assembly at body temperatures lower than the temperature of the parental PNIPAAm-g-HA molecule. Cytotoxicity and acute systemic toxicity assays revealed that P(NIPAAm-co-NtBAAm)-g-HA was not hazardous. The DNA content of chondrogenic differentiated mesenchymal stem/stromal cells (MSCs) embedded in the gels was higher than that of biomaterial-free aggregates during the culture periods. Cartilage-related genes were also expressed in chondrogenic differentiated MSCs embedded in the P (NIPAAm-co-NtBAAm)-g-HA hydrogel. Specifically, an increased expression of SRY-related HMG box-containing gene 9 (Sox9) observed in the hydrogel group compared to controls. These data suggest that P(NIPAAm-co-NtBAAm)-g-HA is a promising injectable scaffold with thermoresponsive properties suitable for in situ cartilage tissue engineering.
基金Project(HNTY2022K03)supported by the Hunan Tieyuan Civil Engineering Testing Co.,Ltd.,ChinaProject(52478573)supported by the National Natural Science Foundation of China。
文摘The seismic damage to ancillary facilities on high-speed railway(HSR)bridges can affect the normal movement of trains.To propose the bridge deck acceleration response spectra of the typical HSR simply-supported girder bridge for simplifying the seismic responses analysis of the facilities on bridges,the finite element models of the HSR multi-span simply-supported girder bridges with CRTSII track were established,and the numerical model was validated by tests.Besides,the effects of the span number,peak ground acceleration(PGA),pier height on the seismic acceleration and response spectra of the bridge deck were investigated.Afterward,the bridge acceleration amplification factor curves and bridge deck response spectra with different PGAs and pier heights were obtained.The formula for bridge deck acceleration amplification factor,with a 95%guarantee rate,was fitted.Moreover,the finite element models of the overhead contact lines(OCL)mounted on rigid base and bridges were established to validate the fitted formula.The results indicated that the maximum seismic acceleration response is in the midspan of the beam.The proposed formula for the bridge deck acceleration response spectra can be used to analyze the earthquake response of the OCL and other ancillary facilities on HSR simply-supported girder bridges.The bridge deck acceleration response spectra are conservative in terms of structural safety and can significantly improving the analysis efficiency.
文摘In this paper,the current situation of agricultural environmental pollution caused by the increase of chemicals input in agriculture in China was analyzed,and it is found that agricultural pollution is related to agricultural industrial policies,urban-rural economic structure,funds input in pollution control,comprehensive environmental management,laws of pollution control,and so forth. To control agricultural pollution effectively,it is needed to implement integration of agricultural and environmental policies,establish environmentally friendly agricultural technology popularizing system,implement integrated planning and management of a basin,and set up and improve legislation to protect agricultural environment.
文摘Engine engineering database system is an oriented C AD applied database management system that has the capability managing distributed data. The paper discusses the security issue of the engine engineering database management system (EDBMS). Through studying and analyzing the database security, to draw a series of securi ty rules, which reach B1, level security standard. Which includes discretionary access control (DAC), mandatory access control (MAC) and audit. The EDBMS implem ents functions of DAC, MAC and multigranularity audit. DAC solves the problems o f role inheritance, right contain, authorization identify and cascade revoke, et c; MAC includes subject and object security setup rule, security modify rule and multilevel relation access operation rule, etc; Audit allows making the sub ject, object or operation type as different audit object to implement flexible a nd multigranularity audit method. The model is designed act as a security agent to access daemon database. At present, the model is implemented which runs on th e Windows 2000 environments.