Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor b...Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor biology and immune responses;however,its specific roles in HCC progression and macrophage-mediated regulation remain unclear.This study aimed to elucidate the biological functions of DNASE1L3 in HCC and to determine how it modulates tumor behavior and immune interactions.Methods:Bioinformatics analyses of the GSE41804 and Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)datasets were used to identify hub genes.Functional assays assessed the impact of DNASE1L3 on HCC cell proliferation,migration,invasion,and cell cycle progression.The effects of DNASE1L3 on macrophage polarization and the Wnt/β-catenin signaling pathway were examined using a co-culture system.An HCC organoid model was established to further validate its regulatory function.Results:Eight prognostic signature genes were identified,with deoxyribonuclease I-like 3(DNase I-like 3)selected as the hub gene.DNASE1L3 overexpression suppressed HCC cell growth,inhibited migration and invasion,induced G1 arrest,and modulated epithelial-mesenchymal transition(EMT)markers.DNASE1L3 knockdown promoted M2-like macrophage polarization.Mechanistically,DNASE1L3 interacted withβ-catenin to enhance its ubiquitination and degradation,thereby inhibiting Wnt/β-catenin signaling and reducing PD-L1 expression.DNASE1L3 overexpression similarly restricted organoid growth and suppressed pathway activity.Conclusion:DNASE1L3 acts as a negative regulator of HCC progression by targeting the Wnt/β-catenin pathway and reducing PD-L1 expression,thereby influencing both tumor cell behavior and macrophage-mediated immune responses.展开更多
By combining data from the Challenging Minisatellite Payload(CHAMP),Swarm-A,and newest Macao Science Satellite-1(MSS-1) missions,we constructed a lithospheric magnetic field model up to spherical harmonic degree N = 1...By combining data from the Challenging Minisatellite Payload(CHAMP),Swarm-A,and newest Macao Science Satellite-1(MSS-1) missions,we constructed a lithospheric magnetic field model up to spherical harmonic degree N = 100.To isolate the lithospheric magnetic field signals,we utilized the latest CHAOS-8(CHAMP,Φrsted,and SAC-C 8) model and MGFM(Multisource Geomagnetic Field Model) to remove nonlithospheric sources,including the core field,magnetospheric field,ocean tidal field,and ocean circulation field.Subsequently,orbit-by-orbit processing was applied to both scalar and vector data,such as spherical harmonic high-pass filtering,singular spectrum analysis,and line leveling,to suppress noise and residual signals along the satellite tracks.With an orbital inclination of only 41°,MSS-1 effectively captures fine-scale lithospheric magnetic field signals in mid-to low-latitude regions.Its data exhibit a root mean square error of only 0.77 nT relative to the final model,confirming the high quality and utility of lithospheric field modeling.The resulting model exhibits excellent consistency with the MF7(Magnetic Field Model 7),maintaining a high correlation up to N = 90 and still exceeding 0.65 at N = 100.These results demonstrate the reliability and value of MSS-1 data in global lithospheric magnetic field modeling.展开更多
Porous liquid-conducting micro-heat exchangers have garnered considerable attention for their role in efficient heat dissipation in small electronic devices.This demand highlights the need for advanced mathematical mo...Porous liquid-conducting micro-heat exchangers have garnered considerable attention for their role in efficient heat dissipation in small electronic devices.This demand highlights the need for advanced mathematical models to optimize the selection of mixed heat exchange media and equipment design.A capillary bundle evaporation model for porous liquid-conducting media was developed based on the conjugate mass transfer evaporation rate prediction model of a single capillary tube,supplemented by mercury injection experimental data.Theoretical and experimental comparisons were conducted using 1,2-propanediol-glycerol(PG-VG)mixtures at molar ratios of 1:9,3:7,5:5,and 7:3 at 120,150,and 180℃.The Jouyban-Acree model was implemented to enhance the evaporation rate predictions.For the 7:3 PG-VG mixture at 180℃under the experimental conditions of the thermal medium,the model's error reduced from 16.75%to 10.84%post-correction.Overall,the mean relative error decreased from 11.76%to 5.98%after correction.展开更多
Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
Fetr6 is an underground mine in which chromite is extracted using stope and pillar mining method. Despite of all improving works such as roof supporting and replacing of ore pillars with concrete pillars, pillar No. 1...Fetr6 is an underground mine in which chromite is extracted using stope and pillar mining method. Despite of all improving works such as roof supporting and replacing of ore pillars with concrete pillars, pillar No. 19 failed and other pillars failed progressively as a domino effect and 4000 m2 of mine collapsed within a few minutes, consequently. For detail investigation, two 3-D numerical models were developed by 3Dec. The first, a base model, was used for estimation of stress on pillars just before failure and the other for investigation of rock burst in pillar No. 19. The results show that discontinuity parameters such as friction angle and shear stiffness is critical parameters in this pillar failure. In addition, it indicates that W/H ratio equal 0.3, the lack of ore extraction strategy and inadequate roof support are the major reasons for this failure. In this paper, the procedure of study was described.展开更多
Traditional feature-based turbine blade models can match the needs of geometric modeling but could hardly meet the requirement of data extraction in 1-D heat transfer analysis. In this paper, the requirements of data ...Traditional feature-based turbine blade models can match the needs of geometric modeling but could hardly meet the requirement of data extraction in 1-D heat transfer analysis. In this paper, the requirements of data extraction in 1-D heat transfer analysis are taken into consideration as well as geometric representation in parametric design process. An improved turbine blade parametric modeling method is proposed. Based on the modeling method proposed, a system structure of blade modeling process considering 1-D heat transfer analysis is devised. Eventually, a turbine blade parametric modeling system is constructed to test and verify the feasibility of the proposed modeling method and system structure. Experiments show that the blade parametric modeling method proposed can make geometric models better adapt to the specific requirements of 1-D heat transfer analysis and has certain reference value to the creation of high quality digital models.展开更多
Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrach...Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrachloride （ CCl4 ） ; Acute liver injury model in mice was induced by aminogalactose （GAIN） or lipopolysaccharide （LPS）. Results In CCl4-induced chronic liver injury model, FDP （1 , 4 g·kg^-1·d^-1, q.d., for 10 weeks） significantly lowered ALT, AST,γ-glutamyl transpeptidase （γ-GT）, alkaline phosphatase （ALP）, and total bilirubin （T-BIL） in serum compared with vehicle; simultaneously it evidently elevated abnormal total protein （TP）, albumin （ALB） and total cholesterol （ T-CHO ） levels in serum; it also dose-dependently reduced hydroxyproline contents in hepatic tissue. 4 g·kg^-1·d^-1 of FDP apparently decreased incidence of hepatic cirrhosis, and alleviated pathological changes of liver tissue. In GaiN-induced model, 1.0 - 4. 0 g·kg^-1·d^-1 of FDP （ bid, for 3 d ） significantly lowered alanine aminotransferase （ ALT ） and aspartate aminotransferase （ AST ） levels in serum ; it also decreased liver coefficient. 4. 0 g·kg^-1·d^-1 of FDP significantly alleviated pathological changes of cell ultra-structures. In LPS-induced model, only high dose of FDP （4. 0 g·kg^-1·d^-1, bid, for 12 d） significantly decreased ALT level in serum. Conclusion This study first demonstrated the protective effect of oral FDP on chronic liver injury caused by CCl4, and confirmed its effect on acute liver injury at the same time, suggesting that Long-term oral FDP is efficacious against liver injury induced by different factors and can be used as an oral liver protective agent in clinic.展开更多
3-D geological modeling plays an increasingly important role in Petroleum Geology, Mining Geology and Engineering Geology. The complexity of geological conditions requires different modeling methods in different situa...3-D geological modeling plays an increasingly important role in Petroleum Geology, Mining Geology and Engineering Geology. The complexity of geological conditions requires different modeling methods in different situations. This paper summarizes the general concept of geological modeling; compares the characteristics of borehole-based modeling, cross-section based modeling and multi- source interactive modeling; analyses key techniques in 3-D geological modeling; and highlights the main difficulties and directions of future studies.展开更多
Applying new approaches, methods, and technologies for the estimation of reserves can effectively improve the efficiency and accuracy of assessments of solid mineral resources. After analyzing the development of 3-D g...Applying new approaches, methods, and technologies for the estimation of reserves can effectively improve the efficiency and accuracy of assessments of solid mineral resources. After analyzing the development of 3-D geoscience modeling technology （3-D GMT）, this paper discusses the application of 3-D GMT for the estimation of solid mineral reserves, emphatically introducing its workflow and two key technologies, 3-D orebody surface modeling, and property modeling. Moreover, the paper analyzes the limitations of traditional methods, such as the section method and geological block method, and points out the advantages of 3-D GMT： building more accurate 3-D orebody models, expressing the internal inhomogeneous attributes of an orebody, reducing the potential for errors in the estimation of reserves, and implementing dynamic estimations of reserves.展开更多
In order to verify the feasibility and stability of a degree-day model on simulating the long time series of glacier mass balance, we apply a degree-day model to simulate the mass balance of Urumqi Glacier No. 1 for t...In order to verify the feasibility and stability of a degree-day model on simulating the long time series of glacier mass balance, we apply a degree-day model to simulate the mass balance of Urumqi Glacier No. 1 for the period 1987/1988-2007/2008 based on temperature and precipitation data from a nearby climate station. The model is calibrated by simulating point measurements of mass bal- ance, mass balance profiles, and mean specific mass balance during 1987/1988-1996/1997. The opti- mized parameters are obtained by using a least square method to make the model fit the measured mass balance through the model calibration. The model validation （1997/1998-2007/2008） indicates that the modeled results are in good agreement with the observations. The static mass balance sensitiv- ity of Urumqi Glacier No. 1 is analyzed by computing the mass balance of the glacier for a temperature increase of 1℃, with and without a 5% precipitation increase, and the values for the east branch are -0.80 and -0.87 m w.e. a-1℃-1, respectively, and for the west branch, the values are -0.68 and -0.74 m w.e. a-1℃-1, respectively. Moreover, the analysis of the parameter stability indicates that the parame- ters in the model determined from the current climate condition can be applied in the prediction of the future mass balance changes for the glacier and provide a reference for extending the model to other small glaciers in western China.展开更多
Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following ...Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups： sham （with the left anterior descending coronary artery exposed but without ligation）, MI （left anterior descending coronary artery ligation）, and MI plus NRG-1 （left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 （10 lag/kg, once daily for 7 days））. At 4 weeks after MI, echocardi- ography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening, mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 （neuronal specific pro- tein）, nerve growth factor, choline acetyltransferase （vagus nerve marker）, and vesicular acetylcholine transporter （cardiac vagal nerve fiber marker） in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG- 1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.展开更多
Earth’s internal core and crustal magnetic fields,as measured by geomagnetic satellites like MSS-1(Macao Science Satellite-1)and Swarm,are vital for understanding core dynamics and tectonic evolution.To model these i...Earth’s internal core and crustal magnetic fields,as measured by geomagnetic satellites like MSS-1(Macao Science Satellite-1)and Swarm,are vital for understanding core dynamics and tectonic evolution.To model these internal magnetic fields accurately,data selection based on specific criteria is often employed to minimize the influence of rapidly changing current systems in the ionosphere and magnetosphere.However,the quantitative impact of various data selection criteria on internal geomagnetic field modeling is not well understood.This study aims to address this issue and provide a reference for constructing and applying geomagnetic field models.First,we collect the latest MSS-1 and Swarm satellite magnetic data and summarize widely used data selection criteria in geomagnetic field modeling.Second,we briefly describe the method to co-estimate the core,crustal,and large-scale magnetospheric fields using satellite magnetic data.Finally,we conduct a series of field modeling experiments with different data selection criteria to quantitatively estimate their influence.Our numerical experiments confirm that without selecting data from dark regions and geomagnetically quiet times,the resulting internal field differences at the Earth’s surface can range from tens to hundreds of nanotesla(nT).Additionally,we find that the uncertainties introduced into field models by different data selection criteria are significantly larger than the measurement accuracy of modern geomagnetic satellites.These uncertainties should be considered when utilizing constructed magnetic field models for scientific research and applications.展开更多
A finite element method is developed for simulating frequency domain electromagnetic responses due to a dipole source in the 2-D conductive structures. Computing costs are considerably minimized by reducing the full t...A finite element method is developed for simulating frequency domain electromagnetic responses due to a dipole source in the 2-D conductive structures. Computing costs are considerably minimized by reducing the full three-dimensional problem to a series of two-dimensional problems. This is accomplished by transforming the problem into y-wave number （Ky） domain using Fourier transform and the y-axis is parallel to the structural strike. In the Ky domain, two coupled partial differential equations for magnetic field Hy and electric field Ey are derived. For a specific value of Ky, the coupled equations are solved by the finite element method with isoparametric elements in the x-z plane. Application of the inverse Fourier transform to the Ky, domain provides the electric and magnetic fields in real space. The equations derived can be applied to general complex two-dimensional structures containing either electric or magnetic dipole source in any direction. In the modeling of the electromagnetic measurement, we adopted a pseudo-delta function to distribute the dipole source current and circumvent the problem of singularity at the source point. Moreover, the suggested method used isoparametric finite elements to accommodate the complex subsurface formation. For the large scale linear system derived from the discretization of the Maxwell＇s equations, several iterative solvers were used and compared to select the optimal one. A quantitative test of accuracy was presented which compared the finite element results with analytic solutions for a dipole source in homogeneous space for different ranges and different wave numbers Ky. to validate the addressed the effects of the distribution range τ of the homogeneous medium. code and check its effectiveness. In addition, we pseudo-delta function on the numerical results in展开更多
We study the localized coherent structures ofa generally nonintegrable (2+ 1 )-dimensional KdV equation via a variable separation approach. In a special integrable case, the entrance of some arbitrary functions leads ...We study the localized coherent structures ofa generally nonintegrable (2+ 1 )-dimensional KdV equation via a variable separation approach. In a special integrable case, the entrance of some arbitrary functions leads to abundant coherent structures. However, in the general nonintegrable case, an additional condition has to be introduced for these arbitrary functions. Although the additional condition has been introduced into the solutions of the nonintegrable KdV equation, there still exist many interesting solitary wave structures. Especially, the nonintegrable KdV equation possesses the breather-like localized excitations, and the similar static ring soliton solutions as in the integrable case. Furthermor,in the integrable case, the interaction between two travelling ring solitons is elastic, while in the nonintegrable case we cannot find even the single travelling ring soliton solution.展开更多
Measurements from geomagnetic satellites continue to underpin advances in geomagnetic field models that describe Earth's internally generated magnetic field.Here,we present a new field model,MSCM,that integrates v...Measurements from geomagnetic satellites continue to underpin advances in geomagnetic field models that describe Earth's internally generated magnetic field.Here,we present a new field model,MSCM,that integrates vector and scalar data from the Swarm,China Seismo-Electromagnetic Satellite(CSES),and Macao Science Satellite-1(MSS-1)missions.The model spans from 2014.0 to 2024.5,incorporating the core,lithospheric,and magnetospheric fields,and it shows characteristics similar to other published models based on different data.For the first time,we demonstrate that it is possible to successfully construct a geomagnetic field model that incorporates CSES vector data,albeit one in which the radial and azimuthal CSES vector components are Huber downweighted.We further show that data from the MSS-1 can be integrated within an explicitly smoothed,fully time-dependent model description.Using the MSCM,we identify new behavior of the South Atlantic Anomaly,the broad region of low magnetic field intensity over the southern Atlantic.This prominent feature appears split into a western part and an eastern part,each with its own intensity minimum.Since 2015,the principal western minimum has undergone only modest intensity decreases of 290 nT and westward motion of 20 km per year,whereas the recently formed eastern minimum has shown a 2–3 times greater intensity drop of 730 nT with no apparent east-west motion.展开更多
基金funded by Shanghai Science and Technology Innovation Action Plan Project(22140901100)Shanghai Key Laboratory of Molecular Imaging(18DZ2260400)Shanghai University of Medicine and Health Science Seed Fund(SSF-24-21-01).
文摘Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor biology and immune responses;however,its specific roles in HCC progression and macrophage-mediated regulation remain unclear.This study aimed to elucidate the biological functions of DNASE1L3 in HCC and to determine how it modulates tumor behavior and immune interactions.Methods:Bioinformatics analyses of the GSE41804 and Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)datasets were used to identify hub genes.Functional assays assessed the impact of DNASE1L3 on HCC cell proliferation,migration,invasion,and cell cycle progression.The effects of DNASE1L3 on macrophage polarization and the Wnt/β-catenin signaling pathway were examined using a co-culture system.An HCC organoid model was established to further validate its regulatory function.Results:Eight prognostic signature genes were identified,with deoxyribonuclease I-like 3(DNase I-like 3)selected as the hub gene.DNASE1L3 overexpression suppressed HCC cell growth,inhibited migration and invasion,induced G1 arrest,and modulated epithelial-mesenchymal transition(EMT)markers.DNASE1L3 knockdown promoted M2-like macrophage polarization.Mechanistically,DNASE1L3 interacted withβ-catenin to enhance its ubiquitination and degradation,thereby inhibiting Wnt/β-catenin signaling and reducing PD-L1 expression.DNASE1L3 overexpression similarly restricted organoid growth and suppressed pathway activity.Conclusion:DNASE1L3 acts as a negative regulator of HCC progression by targeting the Wnt/β-catenin pathway and reducing PD-L1 expression,thereby influencing both tumor cell behavior and macrophage-mediated immune responses.
基金the support of the National Natural Science Foundation of China (Nos. 42250103, 41974073, and 41404053)the Macao Foundation and the preresearch project of Civil Aerospace Technologies (Nos. D020308 and D020303)funded by China’s National Space Administration, and the Specialized Research Fund for State Key Laboratories。
文摘By combining data from the Challenging Minisatellite Payload(CHAMP),Swarm-A,and newest Macao Science Satellite-1(MSS-1) missions,we constructed a lithospheric magnetic field model up to spherical harmonic degree N = 100.To isolate the lithospheric magnetic field signals,we utilized the latest CHAOS-8(CHAMP,Φrsted,and SAC-C 8) model and MGFM(Multisource Geomagnetic Field Model) to remove nonlithospheric sources,including the core field,magnetospheric field,ocean tidal field,and ocean circulation field.Subsequently,orbit-by-orbit processing was applied to both scalar and vector data,such as spherical harmonic high-pass filtering,singular spectrum analysis,and line leveling,to suppress noise and residual signals along the satellite tracks.With an orbital inclination of only 41°,MSS-1 effectively captures fine-scale lithospheric magnetic field signals in mid-to low-latitude regions.Its data exhibit a root mean square error of only 0.77 nT relative to the final model,confirming the high quality and utility of lithospheric field modeling.The resulting model exhibits excellent consistency with the MF7(Magnetic Field Model 7),maintaining a high correlation up to N = 90 and still exceeding 0.65 at N = 100.These results demonstrate the reliability and value of MSS-1 data in global lithospheric magnetic field modeling.
基金the funding support of National Natural Science Foundation of China(21978204)。
文摘Porous liquid-conducting micro-heat exchangers have garnered considerable attention for their role in efficient heat dissipation in small electronic devices.This demand highlights the need for advanced mathematical models to optimize the selection of mixed heat exchange media and equipment design.A capillary bundle evaporation model for porous liquid-conducting media was developed based on the conjugate mass transfer evaporation rate prediction model of a single capillary tube,supplemented by mercury injection experimental data.Theoretical and experimental comparisons were conducted using 1,2-propanediol-glycerol(PG-VG)mixtures at molar ratios of 1:9,3:7,5:5,and 7:3 at 120,150,and 180℃.The Jouyban-Acree model was implemented to enhance the evaporation rate predictions.For the 7:3 PG-VG mixture at 180℃under the experimental conditions of the thermal medium,the model's error reduced from 16.75%to 10.84%post-correction.Overall,the mean relative error decreased from 11.76%to 5.98%after correction.
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
文摘Fetr6 is an underground mine in which chromite is extracted using stope and pillar mining method. Despite of all improving works such as roof supporting and replacing of ore pillars with concrete pillars, pillar No. 19 failed and other pillars failed progressively as a domino effect and 4000 m2 of mine collapsed within a few minutes, consequently. For detail investigation, two 3-D numerical models were developed by 3Dec. The first, a base model, was used for estimation of stress on pillars just before failure and the other for investigation of rock burst in pillar No. 19. The results show that discontinuity parameters such as friction angle and shear stiffness is critical parameters in this pillar failure. In addition, it indicates that W/H ratio equal 0.3, the lack of ore extraction strategy and inadequate roof support are the major reasons for this failure. In this paper, the procedure of study was described.
文摘Traditional feature-based turbine blade models can match the needs of geometric modeling but could hardly meet the requirement of data extraction in 1-D heat transfer analysis. In this paper, the requirements of data extraction in 1-D heat transfer analysis are taken into consideration as well as geometric representation in parametric design process. An improved turbine blade parametric modeling method is proposed. Based on the modeling method proposed, a system structure of blade modeling process considering 1-D heat transfer analysis is devised. Eventually, a turbine blade parametric modeling system is constructed to test and verify the feasibility of the proposed modeling method and system structure. Experiments show that the blade parametric modeling method proposed can make geometric models better adapt to the specific requirements of 1-D heat transfer analysis and has certain reference value to the creation of high quality digital models.
文摘Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrachloride （ CCl4 ） ; Acute liver injury model in mice was induced by aminogalactose （GAIN） or lipopolysaccharide （LPS）. Results In CCl4-induced chronic liver injury model, FDP （1 , 4 g·kg^-1·d^-1, q.d., for 10 weeks） significantly lowered ALT, AST,γ-glutamyl transpeptidase （γ-GT）, alkaline phosphatase （ALP）, and total bilirubin （T-BIL） in serum compared with vehicle; simultaneously it evidently elevated abnormal total protein （TP）, albumin （ALB） and total cholesterol （ T-CHO ） levels in serum; it also dose-dependently reduced hydroxyproline contents in hepatic tissue. 4 g·kg^-1·d^-1 of FDP apparently decreased incidence of hepatic cirrhosis, and alleviated pathological changes of liver tissue. In GaiN-induced model, 1.0 - 4. 0 g·kg^-1·d^-1 of FDP （ bid, for 3 d ） significantly lowered alanine aminotransferase （ ALT ） and aspartate aminotransferase （ AST ） levels in serum ; it also decreased liver coefficient. 4. 0 g·kg^-1·d^-1 of FDP significantly alleviated pathological changes of cell ultra-structures. In LPS-induced model, only high dose of FDP （4. 0 g·kg^-1·d^-1, bid, for 12 d） significantly decreased ALT level in serum. Conclusion This study first demonstrated the protective effect of oral FDP on chronic liver injury caused by CCl4, and confirmed its effect on acute liver injury at the same time, suggesting that Long-term oral FDP is efficacious against liver injury induced by different factors and can be used as an oral liver protective agent in clinic.
文摘3-D geological modeling plays an increasingly important role in Petroleum Geology, Mining Geology and Engineering Geology. The complexity of geological conditions requires different modeling methods in different situations. This paper summarizes the general concept of geological modeling; compares the characteristics of borehole-based modeling, cross-section based modeling and multi- source interactive modeling; analyses key techniques in 3-D geological modeling; and highlights the main difficulties and directions of future studies.
文摘Applying new approaches, methods, and technologies for the estimation of reserves can effectively improve the efficiency and accuracy of assessments of solid mineral resources. After analyzing the development of 3-D geoscience modeling technology （3-D GMT）, this paper discusses the application of 3-D GMT for the estimation of solid mineral reserves, emphatically introducing its workflow and two key technologies, 3-D orebody surface modeling, and property modeling. Moreover, the paper analyzes the limitations of traditional methods, such as the section method and geological block method, and points out the advantages of 3-D GMT： building more accurate 3-D orebody models, expressing the internal inhomogeneous attributes of an orebody, reducing the potential for errors in the estimation of reserves, and implementing dynamic estimations of reserves.
基金supported by the Knowledge Innovation Project of the Chinese Academy of Sciences (No. KZCX2-EW-311)the National Basic Research Program of China (No. 2007CB411501)the National Natural Science Foundation of China (Nos. 1141001040, J0930003/J0109)
文摘In order to verify the feasibility and stability of a degree-day model on simulating the long time series of glacier mass balance, we apply a degree-day model to simulate the mass balance of Urumqi Glacier No. 1 for the period 1987/1988-2007/2008 based on temperature and precipitation data from a nearby climate station. The model is calibrated by simulating point measurements of mass bal- ance, mass balance profiles, and mean specific mass balance during 1987/1988-1996/1997. The opti- mized parameters are obtained by using a least square method to make the model fit the measured mass balance through the model calibration. The model validation （1997/1998-2007/2008） indicates that the modeled results are in good agreement with the observations. The static mass balance sensitiv- ity of Urumqi Glacier No. 1 is analyzed by computing the mass balance of the glacier for a temperature increase of 1℃, with and without a 5% precipitation increase, and the values for the east branch are -0.80 and -0.87 m w.e. a-1℃-1, respectively, and for the west branch, the values are -0.68 and -0.74 m w.e. a-1℃-1, respectively. Moreover, the analysis of the parameter stability indicates that the parame- ters in the model determined from the current climate condition can be applied in the prediction of the future mass balance changes for the glacier and provide a reference for extending the model to other small glaciers in western China.
基金supported by a grant from the National Key Basic Research Development Program,the“973”Program,No.2012CB518604the National Natural Science Foundation of China,No.81260052+1 种基金the Natural Science Foundation of Hubei Province,No.2014CKB497,2014BKB075,and 2015BKA339the Natural Science Foundation of Henan Province of China,No.201602262
文摘Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups： sham （with the left anterior descending coronary artery exposed but without ligation）, MI （left anterior descending coronary artery ligation）, and MI plus NRG-1 （left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 （10 lag/kg, once daily for 7 days））. At 4 weeks after MI, echocardi- ography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening, mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 （neuronal specific pro- tein）, nerve growth factor, choline acetyltransferase （vagus nerve marker）, and vesicular acetylcholine transporter （cardiac vagal nerve fiber marker） in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG- 1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.
基金supported by the National Natural Science Foundation of China(42250101)the Macao Foundation。
文摘Earth’s internal core and crustal magnetic fields,as measured by geomagnetic satellites like MSS-1(Macao Science Satellite-1)and Swarm,are vital for understanding core dynamics and tectonic evolution.To model these internal magnetic fields accurately,data selection based on specific criteria is often employed to minimize the influence of rapidly changing current systems in the ionosphere and magnetosphere.However,the quantitative impact of various data selection criteria on internal geomagnetic field modeling is not well understood.This study aims to address this issue and provide a reference for constructing and applying geomagnetic field models.First,we collect the latest MSS-1 and Swarm satellite magnetic data and summarize widely used data selection criteria in geomagnetic field modeling.Second,we briefly describe the method to co-estimate the core,crustal,and large-scale magnetospheric fields using satellite magnetic data.Finally,we conduct a series of field modeling experiments with different data selection criteria to quantitatively estimate their influence.Our numerical experiments confirm that without selecting data from dark regions and geomagnetically quiet times,the resulting internal field differences at the Earth’s surface can range from tens to hundreds of nanotesla(nT).Additionally,we find that the uncertainties introduced into field models by different data selection criteria are significantly larger than the measurement accuracy of modern geomagnetic satellites.These uncertainties should be considered when utilizing constructed magnetic field models for scientific research and applications.
文摘A finite element method is developed for simulating frequency domain electromagnetic responses due to a dipole source in the 2-D conductive structures. Computing costs are considerably minimized by reducing the full three-dimensional problem to a series of two-dimensional problems. This is accomplished by transforming the problem into y-wave number （Ky） domain using Fourier transform and the y-axis is parallel to the structural strike. In the Ky domain, two coupled partial differential equations for magnetic field Hy and electric field Ey are derived. For a specific value of Ky, the coupled equations are solved by the finite element method with isoparametric elements in the x-z plane. Application of the inverse Fourier transform to the Ky, domain provides the electric and magnetic fields in real space. The equations derived can be applied to general complex two-dimensional structures containing either electric or magnetic dipole source in any direction. In the modeling of the electromagnetic measurement, we adopted a pseudo-delta function to distribute the dipole source current and circumvent the problem of singularity at the source point. Moreover, the suggested method used isoparametric finite elements to accommodate the complex subsurface formation. For the large scale linear system derived from the discretization of the Maxwell＇s equations, several iterative solvers were used and compared to select the optimal one. A quantitative test of accuracy was presented which compared the finite element results with analytic solutions for a dipole source in homogeneous space for different ranges and different wave numbers Ky. to validate the addressed the effects of the distribution range τ of the homogeneous medium. code and check its effectiveness. In addition, we pseudo-delta function on the numerical results in
文摘We study the localized coherent structures ofa generally nonintegrable (2+ 1 )-dimensional KdV equation via a variable separation approach. In a special integrable case, the entrance of some arbitrary functions leads to abundant coherent structures. However, in the general nonintegrable case, an additional condition has to be introduced for these arbitrary functions. Although the additional condition has been introduced into the solutions of the nonintegrable KdV equation, there still exist many interesting solitary wave structures. Especially, the nonintegrable KdV equation possesses the breather-like localized excitations, and the similar static ring soliton solutions as in the integrable case. Furthermor,in the integrable case, the interaction between two travelling ring solitons is elastic, while in the nonintegrable case we cannot find even the single travelling ring soliton solution.
基金supported by the National Natural Science Foundation of China(Grant No.42274003)PWL was supported by Swarm DISC(Swarm Data,Innovation,and Science Cluster)+2 种基金funded by the European Space Agency(ESAContract No.4000109587)HFR acknowledges funding from the UK Natural Environment Research Council(Grant No.NE/V010867/1)。
文摘Measurements from geomagnetic satellites continue to underpin advances in geomagnetic field models that describe Earth's internally generated magnetic field.Here,we present a new field model,MSCM,that integrates vector and scalar data from the Swarm,China Seismo-Electromagnetic Satellite(CSES),and Macao Science Satellite-1(MSS-1)missions.The model spans from 2014.0 to 2024.5,incorporating the core,lithospheric,and magnetospheric fields,and it shows characteristics similar to other published models based on different data.For the first time,we demonstrate that it is possible to successfully construct a geomagnetic field model that incorporates CSES vector data,albeit one in which the radial and azimuthal CSES vector components are Huber downweighted.We further show that data from the MSS-1 can be integrated within an explicitly smoothed,fully time-dependent model description.Using the MSCM,we identify new behavior of the South Atlantic Anomaly,the broad region of low magnetic field intensity over the southern Atlantic.This prominent feature appears split into a western part and an eastern part,each with its own intensity minimum.Since 2015,the principal western minimum has undergone only modest intensity decreases of 290 nT and westward motion of 20 km per year,whereas the recently formed eastern minimum has shown a 2–3 times greater intensity drop of 730 nT with no apparent east-west motion.
