Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological b...Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.展开更多
Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to human...Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to humans.However,the development of genetically engineered hamsters has lagged behind that of mice and rats,largely because of an embryonic development block at the two-cell stage in vitro.Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters,precise DNA fragment insertion or conditional knockout(cKO)models have not previously been reported,likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair(HDR).Methods:In this study,we generated conditional alleles of the ApoF gene in golden Syrian hamsters.A two-cut strategy was applied using Cas9 protein,two sgRNAs,and a single donor plasmid containing exon 2 flanked by loxP sites and two~0.8 kb homology arms.A mixture of Cas9 protein,sgRNAs,and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.Results:The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%,and the genetically modified floxed alleles were successfully transmitted through the germline.The functionality of the inserted loxP sites was validated by in vivo Cremediated recombination following local administration of AAV vectors,including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.Conclusions:To our knowledge,this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster,providing a valuable tool for mechanistic studies of gene function and disease modeling.展开更多
In this article,we show the existence,uniqueness and stability of bounded solutions to the following quasilinear problems with mean curvature operator(φ'(x′(t)))′=f(t,x),t≥t_(0),lim_(t→∞)x(t)=ψ_(0),lim_(t→...In this article,we show the existence,uniqueness and stability of bounded solutions to the following quasilinear problems with mean curvature operator(φ'(x′(t)))′=f(t,x),t≥t_(0),lim_(t→∞)x(t)=ψ_(0),lim_(t→∞)x′(t)e^(t)=0,where t_(0) and ψ_(0) are real constants,φ(s)=s/√1−s^(2),s∈R with s∈(−1,1),f:[t_(0),∞)×R→R satisfies the Lipschitz or Osgood-type conditions.展开更多
The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from...The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.展开更多
In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary c...In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary conditions on the flat bottom.Assuming“Reynolds roughness regime”,in which the thickness of the domain is very small compared to the wavelength of the roughness(i.e.a very slight roughness),we rigorously derive a generalized Reynolds equation for pressure,clearly showing the roughness-induced effects.Moreover,we give expressions for the average velocity and microrotation.展开更多
The main purpose of using geothermal energy piles(GEPs)is to enable the exploitation of geothermal energy for meeting the heating/cooling demands of buildings efficiently.However,the installation process of convention...The main purpose of using geothermal energy piles(GEPs)is to enable the exploitation of geothermal energy for meeting the heating/cooling demands of buildings efficiently.However,the installation process of conventional GEPs is inconvenient compared with that of traditional foundation piles.The pre-bored grouted planted geothermal energy pile(PGP GEP)is an innovative technology to simplify the installation process.Most investigations of in-situ experiments for conventional GEPs have focused on summer conditions.An in-situ test for a PGP GEP was conducted to analyze the temperature changes and thermo-mechanical characteristics under winter conditions.The results show that the average temperature of the pile decreased by 5.1℃,and the pile exhibited a general trend of high temperatures at both ends and low temperatures in the middle.In mechanics,strong pile end restraints resulted in smaller observed axial strain and higher axial thermal-induced force in the pile ends than at the middle of the pile.展开更多
Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of...Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of user preferences.To address this,we propose a Conditional Generative Adversarial Network(CGAN)that generates diverse and highly relevant itineraries.Our approach begins by constructing a conditional vector that encapsulates a user’s profile.This vector uniquely fuses embeddings from a Heterogeneous Information Network(HIN)to model complex user-place-route relationships,a Recurrent Neural Network(RNN)to capture sequential path dynamics,and Neural Collaborative Filtering(NCF)to incorporate collaborative signals from the wider user base.This comprehensive condition,further enhanced with features representing user interaction confidence and uncertainty,steers a CGAN stabilized by spectral normalization to generate high-fidelity latent route representations,effectively mitigating the data sparsity problem.Recommendations are then formulated using an Anchor-and-Expand algorithm,which selects relevant starting Points of Interest(POI)based on user history,then expands routes through latent similarity matching and geographic coherence optimization,culminating in Traveling Salesman Problem(TSP)-based route optimization for practical travel distances.Experiments on a real-world check-in dataset validate our model’s unique generative capability,achieving F1 scores ranging from 0.163 to 0.305,and near-zero pairs−F1 scores between 0.002 and 0.022.These results confirm the model’s success in generating novel travel routes by recommending new locations and sequences rather than replicating users’past itineraries.This work provides a robust solution for personalized travel planning,capable of generating novel and compelling routes for both new and existing users by learning from collective travel intelligence.展开更多
Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
It is well recognized that Structural Health Monitoring(SHM)reliability evaluation is a key aspect that needs to be urgently addressed to promote the wide application of SHM methods.However,the existing studies typica...It is well recognized that Structural Health Monitoring(SHM)reliability evaluation is a key aspect that needs to be urgently addressed to promote the wide application of SHM methods.However,the existing studies typically transfer the Non-Destructive Testing/Evaluation(NDT/E)reliability metrics to SHM without a systematic analysis of where these metrics originated.Seldom attentions are paid to the evaluation conditions which are very important to apply these metrics.Aimed at this issue,a new condition control-based Dual-Reliability Evaluation(Dual-RE)method for SHM is proposed.This new method is proposed based on a systematic analysis of the whole framework of reliability evaluation from instrument to NDT,and emphasis is paid to the evaluation condition control.Based on these analyses,considering the special online application scenario of SHM,the proposed Dual-RE method contains two key components:Integrated Sensor-based SHM-RE(IS-SHM-RE)and Critical Service Condition-based SHM-RE(CSC-SHM-RE).ISSHM-RE evaluates the reliability of integrated SHM sensor and system themselves under approximate repeatability conditions,while CSC-SHM-RE assesses SHM reliability under the dominant uncertainties during service,namely intermediate conditions.To demonstrate the Dual-RE,crack monitoring by using the Guided Wave-based-SHM(GW-SHM)on aircraft lug structures is taken as a case study.Both the crack detection and sizing performance are evaluated from accuracy and uncertainty.展开更多
The real-time and accurate calculation of electricity indirect carbon emissions is not only the critical component for quantifying the carbon emission levels of the power system but also an effective mean to guide ele...The real-time and accurate calculation of electricity indirect carbon emissions is not only the critical component for quantifying the carbon emission levels of the power system but also an effective mean to guide electricity users in carbon reduction and promote power industry low-carbon transformation.Fundamentally,calculating indirect carbon emissions involves allocating direct carbon emission data from the power source side,indicating that accurate indirect emission results rely on the precise measurement of power source emissions.However,existing research on indirect carbon emissions in large-scale power systems rarely accounts for variations in carbon emission characteristics under different operating conditions of power sources,such as rated/non-rated operating conditions and ramping up/down conditions,making it difficult to reflect source-side and load-side carbon emission information variation during providing ancillary services.Quadratic and exponential functions are proposed to characterize the energy consumption profiles of coal-fired and gas-fired power generation,respectively,to construct a refined carbon emission model for power sources.By leveraging the theory of power system carbon flow,we analyze how variable operating conditions of power sources impact indirect carbon emissions.Case studies demonstrate that changes in power source emissions under variable conditions have a significant effect on the indirect carbon emissions of power grids.展开更多
The internal flow fields within a three-dimensional inward-tunning combined inlet are extremely complex,especially during the engine mode transition,where the tunnel changes may impact the flow fields significantly.To...The internal flow fields within a three-dimensional inward-tunning combined inlet are extremely complex,especially during the engine mode transition,where the tunnel changes may impact the flow fields significantly.To develop an efficient flow field reconstruction model for this,we present an Improved Conditional Denoising Diffusion Generative Adversarial Network(ICDDGAN),which integrates Conditional Denoising Diffusion Probabilistic Models(CDDPMs)with Style GAN,and introduce a reconstruction discrimination mechanism and dynamic loss weight learning strategy.We establish the Mach number flow field dataset by numerical simulation at various backpressures for the mode transition process from turbine mode to ejector ramjet mode at Mach number 2.5.The proposed ICDDGAN model,given only sparse parameter information,can rapidly generate high-quality Mach number flow fields without a large number of samples for training.The results show that ICDDGAN is superior to CDDGAN in terms of training convergence and stability.Moreover,the interpolation and extrapolation test results during backpressure conditions show that ICDDGAN can accurately and quickly reconstruct Mach number fields at various tunnel slice shapes,with a Structural Similarity Index Measure(SSIM)of over 0.96 and a Mean-Square Error(MSE)of 0.035%to actual flow fields,reducing time costs by 7-8 orders of magnitude compared to Computational Fluid Dynamics(CFD)calculations.This can provide an efficient means for rapid computation of complex flow fields.展开更多
County economies form a distinctive,integrated regional economic structure.Their growth is shaped by specific social and historical conditions and,in turn,influences many aspects of wider economic and social developme...County economies form a distinctive,integrated regional economic structure.Their growth is shaped by specific social and historical conditions and,in turn,influences many aspects of wider economic and social development.In China's modernization process,they have always played a vital role.The 2024 Central Economic Work Conference placed strong emphasis on vigorously developing county economies.展开更多
Ti(C,N)-Mo_(2)C-Ni cermet as alternative materials was explored for use in alkaline conditions,replacing the WC-Co cemented carbides,since Co is classified as a potentially carcinogenic substance and there is potentia...Ti(C,N)-Mo_(2)C-Ni cermet as alternative materials was explored for use in alkaline conditions,replacing the WC-Co cemented carbides,since Co is classified as a potentially carcinogenic substance and there is potential hazard of“hard metal disease”under the exposure to cobalt dust.The changes in microstructure,corrosion rate and volumetric loss rate of the two materials were compared under electrochemical corrosion and erosion-corrosion in alkaline environment.The results demonstrates that Ti(C,N)-Mo_(2)C-Ni cermet undergoes passivation when exposed to electrochemical corrosion of NaOH solution,resulting in a significant increase in oxygen content on the corroded surface.The corrosion rate of cermet is approximately one order of magnitude lower than that of the cemented carbide.Under the erosion-corrosion of an alkaline sand-water mixture,both the cermet and cemented carbide experience a gradual increase in volumetric loss rate with prolonging the erosion time.During erosion,the rim phase in cermet is fragile,so cracks easily penetrate it while the core phase remains intact.The medium-grained cemented carbide commonly demonstrates transgranular fracture mode,while in the fine-grained cemented carbide,cracks tend to propagate along phase boundaries.The erosive wear and damage caused by sand particles play a predominant role in the erosion-corrosion process of alkaline sand-water mixtures.This process represents an accelerated destructive phenomenon influenced and intensified by the combined effects of corrosion and erosion.It is confirmed that using cermet as an alternative anti-wear material to cemented carbides is feasible under alkaline conditions,and even better.展开更多
Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
Actuator faults can be critical in turbofan engines as they can lead to stall,surge,loss of thrust and failure of speed control.Thus,fault diagnosis of gas turbine actuators has attracted considerable attention,from b...Actuator faults can be critical in turbofan engines as they can lead to stall,surge,loss of thrust and failure of speed control.Thus,fault diagnosis of gas turbine actuators has attracted considerable attention,from both academia and industry.However,the extensive literature that exists on this topic does not address identifying the severity of actuator faults and focuses mainly on actuator fault detection and isolation.In addition,previous studies of actuator fault identification have not dealt with multiple concurrent faults in real time,especially when these are accompanied by sudden failures under dynamic conditions.This study develops component-level models for fault identification in four typical actuators used in high-bypass ratio turbofan engines under both dynamic and steady-state conditions and these are then integrated with the engine performance model developed by the authors.The research results reported here present a novel method of quantifying actuator faults using dynamic effect compensation.The maximum error for each actuator is less than0.06%and 0.07%,with average computational time of less than 0.0058 s and 0.0086 s for steady-state and transient cases,respectively.These results confirm that the proposed method can accurately and efficiently identify concurrent actuator fault for an engine operating under either transient or steady-state conditions,even in the case of a sudden malfunction.The research results emonstrate the potential benefit to emergency response capabilities by introducing this method of monitoring the health of aero engines.展开更多
In cold regions,rock structures will be weakened by freeze-thaw cycles under various water immersion conditions.Determining how water immersion conditions impact rock deterioration under freeze-thaw cycles is critical...In cold regions,rock structures will be weakened by freeze-thaw cycles under various water immersion conditions.Determining how water immersion conditions impact rock deterioration under freeze-thaw cycles is critical to assess accurately the frost resistance of engineered rock.In this paper,freeze-thaw cycles(temperature range of-20℃-20℃)were performed on the sandstones in different water immersion conditions(fully,partially and non-immersed in water).Then,computed tomography(CT)tests were conducted on the sandstones when the freeze-thaw number reached 0,5,10,15,20 and 30.Next,the effects of water immersion conditions on the microstructure deterioration of sandstone under freezethaw cycles were evaluated using CT spatial imaging,porosity and damage factor.Finally,focusing on the partially immersed condition,the immersion volume rate was defined to understand the effects of immersion degree on the freeze-thaw damage of sandstone and to propose a damage model considering the freeze-thaw number and immersion degree.The results show that with increasing freeze-thaw number,the porosities and damage factors under fully and partially immersed conditions increase continuously,while those under non-immersed condition first increase and then remain approximately constant.The most severe freeze-thaw damage occurs in fully immersed condition,followed by partially immersed condition and finally non-immersed condition.Interestingly,the freeze-thaw number and the immersion volume rate both impact the microstructure deterioration of the partially immersed sandstone.For the same freeze-thaw number,the damage factor increases approximately linearly with increasing immersion volume rate,and the increasing immersion degree exacerbates the microstructure deterioration of sandstone.Moreover,the proposed model can effectively estimate the freeze-thaw damage of partially immersed sandstone with different immersion volume rates.展开更多
The potential of 2-amino-1-propanol(AP)as a novel depressant in selectively floating ilmenite from titanaugite under weakly acidic conditions was investigated.Micro-flotation results show that AP significantly reduces...The potential of 2-amino-1-propanol(AP)as a novel depressant in selectively floating ilmenite from titanaugite under weakly acidic conditions was investigated.Micro-flotation results show that AP significantly reduces the recovery of titanaugite while having no evident impact on ilmenite flotation.Subsequent bench-scale flotation tests further confirm a remarkable improvement in separation efficiency upon the introduction of AP.Contact angle and adsorption tests reveal a stronger affinity of AP towards the titanaugite surface in comparison to ilmenite.Zeta potential measurements and X-ray photoelectron spectroscopy(XPS)analyses exhibit favorable adsorption characteristics of AP on titanaugite,resulting from a synergy of electrostatic attraction and chemical interaction.In contrast,electrostatic repulsion hinders any significant interaction between AP and the ilmenite surface.These findings highlight the potential of AP as a highly efficient depressant for ilmenite flotation,paving the way for reduced reliance on sulfuric acid in the industry.展开更多
Landslide susceptibility prediction(LSP)is significantly affected by the uncertainty issue of landslide related conditioning factor selection.However,most of literature only performs comparative studies on a certain c...Landslide susceptibility prediction(LSP)is significantly affected by the uncertainty issue of landslide related conditioning factor selection.However,most of literature only performs comparative studies on a certain conditioning factor selection method rather than systematically study this uncertainty issue.Targeted,this study aims to systematically explore the influence rules of various commonly used conditioning factor selection methods on LSP,and on this basis to innovatively propose a principle with universal application for optimal selection of conditioning factors.An'yuan County in southern China is taken as example considering 431 landslides and 29 types of conditioning factors.Five commonly used factor selection methods,namely,the correlation analysis(CA),linear regression(LR),principal component analysis(PCA),rough set(RS)and artificial neural network(ANN),are applied to select the optimal factor combinations from the original 29 conditioning factors.The factor selection results are then used as inputs of four types of common machine learning models to construct 20 types of combined models,such as CA-multilayer perceptron,CA-random forest.Additionally,multifactor-based multilayer perceptron random forest models that selecting conditioning factors based on the proposed principle of“accurate data,rich types,clear significance,feasible operation and avoiding duplication”are constructed for comparisons.Finally,the LSP uncertainties are evaluated by the accuracy,susceptibility index distribution,etc.Results show that:(1)multifactor-based models have generally higher LSP performance and lower uncertainties than those of factors selection-based models;(2)Influence degree of different machine learning on LSP accuracy is greater than that of different factor selection methods.Conclusively,the above commonly used conditioning factor selection methods are not ideal for improving LSP performance and may complicate the LSP processes.In contrast,a satisfied combination of conditioning factors can be constructed according to the proposed principle.展开更多
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
基金State Key Laboratory Special Fund,Grant/Award Number:2060204Open Research Project in State Key Laboratory of Vascular Homeostasis and Remodeling,Grant/Award Number:Peking University,202411+3 种基金The Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01Haihe Laboratory of Cell Ecosystem Innovation Fund,Grant/Award Number:HH24KYZX0007CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-024,2022-I2M-1-020 and 2023-I2M-2-001the National Key Research and Development Program of China from the Ministry of Science and Technology,Grant/Award Number:2021YFF0702802。
文摘Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to humans.However,the development of genetically engineered hamsters has lagged behind that of mice and rats,largely because of an embryonic development block at the two-cell stage in vitro.Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters,precise DNA fragment insertion or conditional knockout(cKO)models have not previously been reported,likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair(HDR).Methods:In this study,we generated conditional alleles of the ApoF gene in golden Syrian hamsters.A two-cut strategy was applied using Cas9 protein,two sgRNAs,and a single donor plasmid containing exon 2 flanked by loxP sites and two~0.8 kb homology arms.A mixture of Cas9 protein,sgRNAs,and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.Results:The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%,and the genetically modified floxed alleles were successfully transmitted through the germline.The functionality of the inserted loxP sites was validated by in vivo Cremediated recombination following local administration of AAV vectors,including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.Conclusions:To our knowledge,this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster,providing a valuable tool for mechanistic studies of gene function and disease modeling.
基金Supported by the National Natural Science Foundation of China(Grant Nos.12361040,12061064)the National Science Foundation of Gansu Province(Grant No.22JR5RA264)State Scholarship Fund(Grant No.20230862021).
文摘In this article,we show the existence,uniqueness and stability of bounded solutions to the following quasilinear problems with mean curvature operator(φ'(x′(t)))′=f(t,x),t≥t_(0),lim_(t→∞)x(t)=ψ_(0),lim_(t→∞)x′(t)e^(t)=0,where t_(0) and ψ_(0) are real constants,φ(s)=s/√1−s^(2),s∈R with s∈(−1,1),f:[t_(0),∞)×R→R satisfies the Lipschitz or Osgood-type conditions.
基金supported by the National Natural Science Foundation of China(No.52388102)the Sichuan Science and Technology Program(No.2024NSFTD0011)the Fundamental Research Funds for the State Key Laboratory of Rail Transit Vehicle System of Southwest Jiaotong University(No.2023TPL-T11).
文摘The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.
文摘In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary conditions on the flat bottom.Assuming“Reynolds roughness regime”,in which the thickness of the domain is very small compared to the wavelength of the roughness(i.e.a very slight roughness),we rigorously derive a generalized Reynolds equation for pressure,clearly showing the roughness-induced effects.Moreover,we give expressions for the average velocity and microrotation.
文摘The main purpose of using geothermal energy piles(GEPs)is to enable the exploitation of geothermal energy for meeting the heating/cooling demands of buildings efficiently.However,the installation process of conventional GEPs is inconvenient compared with that of traditional foundation piles.The pre-bored grouted planted geothermal energy pile(PGP GEP)is an innovative technology to simplify the installation process.Most investigations of in-situ experiments for conventional GEPs have focused on summer conditions.An in-situ test for a PGP GEP was conducted to analyze the temperature changes and thermo-mechanical characteristics under winter conditions.The results show that the average temperature of the pile decreased by 5.1℃,and the pile exhibited a general trend of high temperatures at both ends and low temperatures in the middle.In mechanics,strong pile end restraints resulted in smaller observed axial strain and higher axial thermal-induced force in the pile ends than at the middle of the pile.
基金supported by the Chung-Ang University Research Grants in 2023.Alsothe work is supported by the ELLIIT Excellence Center at Linköping–Lund in Information Technology in Sweden.
文摘Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of user preferences.To address this,we propose a Conditional Generative Adversarial Network(CGAN)that generates diverse and highly relevant itineraries.Our approach begins by constructing a conditional vector that encapsulates a user’s profile.This vector uniquely fuses embeddings from a Heterogeneous Information Network(HIN)to model complex user-place-route relationships,a Recurrent Neural Network(RNN)to capture sequential path dynamics,and Neural Collaborative Filtering(NCF)to incorporate collaborative signals from the wider user base.This comprehensive condition,further enhanced with features representing user interaction confidence and uncertainty,steers a CGAN stabilized by spectral normalization to generate high-fidelity latent route representations,effectively mitigating the data sparsity problem.Recommendations are then formulated using an Anchor-and-Expand algorithm,which selects relevant starting Points of Interest(POI)based on user history,then expands routes through latent similarity matching and geographic coherence optimization,culminating in Traveling Salesman Problem(TSP)-based route optimization for practical travel distances.Experiments on a real-world check-in dataset validate our model’s unique generative capability,achieving F1 scores ranging from 0.163 to 0.305,and near-zero pairs−F1 scores between 0.002 and 0.022.These results confirm the model’s success in generating novel travel routes by recommending new locations and sequences rather than replicating users’past itineraries.This work provides a robust solution for personalized travel planning,capable of generating novel and compelling routes for both new and existing users by learning from collective travel intelligence.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
基金the support from National Natural Science Foundation of China(No.52275153)the Frontier Technologies R&D Program of Jiangsu,China(No.BF2024068)+1 种基金The Fund of Prospective Layout of Scientific Research for Nanjing University of Aeronautics and Astronautics,ChinaResearch Fund of State Key Laboratory of Mechanics and Control for Aerospace Structures(Nanjing University of Aeronautics and Astronautics),China(Nos.MCAS-I-0425K01,MCAS-I-0423G01)。
文摘It is well recognized that Structural Health Monitoring(SHM)reliability evaluation is a key aspect that needs to be urgently addressed to promote the wide application of SHM methods.However,the existing studies typically transfer the Non-Destructive Testing/Evaluation(NDT/E)reliability metrics to SHM without a systematic analysis of where these metrics originated.Seldom attentions are paid to the evaluation conditions which are very important to apply these metrics.Aimed at this issue,a new condition control-based Dual-Reliability Evaluation(Dual-RE)method for SHM is proposed.This new method is proposed based on a systematic analysis of the whole framework of reliability evaluation from instrument to NDT,and emphasis is paid to the evaluation condition control.Based on these analyses,considering the special online application scenario of SHM,the proposed Dual-RE method contains two key components:Integrated Sensor-based SHM-RE(IS-SHM-RE)and Critical Service Condition-based SHM-RE(CSC-SHM-RE).ISSHM-RE evaluates the reliability of integrated SHM sensor and system themselves under approximate repeatability conditions,while CSC-SHM-RE assesses SHM reliability under the dominant uncertainties during service,namely intermediate conditions.To demonstrate the Dual-RE,crack monitoring by using the Guided Wave-based-SHM(GW-SHM)on aircraft lug structures is taken as a case study.Both the crack detection and sizing performance are evaluated from accuracy and uncertainty.
基金supported by the Science and Technology Project of China Southern Power Grid Co.,Ltd.(ZBKTM20232244)the Project of National Natural of Science Foundation of China(52477103).
文摘The real-time and accurate calculation of electricity indirect carbon emissions is not only the critical component for quantifying the carbon emission levels of the power system but also an effective mean to guide electricity users in carbon reduction and promote power industry low-carbon transformation.Fundamentally,calculating indirect carbon emissions involves allocating direct carbon emission data from the power source side,indicating that accurate indirect emission results rely on the precise measurement of power source emissions.However,existing research on indirect carbon emissions in large-scale power systems rarely accounts for variations in carbon emission characteristics under different operating conditions of power sources,such as rated/non-rated operating conditions and ramping up/down conditions,making it difficult to reflect source-side and load-side carbon emission information variation during providing ancillary services.Quadratic and exponential functions are proposed to characterize the energy consumption profiles of coal-fired and gas-fired power generation,respectively,to construct a refined carbon emission model for power sources.By leveraging the theory of power system carbon flow,we analyze how variable operating conditions of power sources impact indirect carbon emissions.Case studies demonstrate that changes in power source emissions under variable conditions have a significant effect on the indirect carbon emissions of power grids.
文摘The internal flow fields within a three-dimensional inward-tunning combined inlet are extremely complex,especially during the engine mode transition,where the tunnel changes may impact the flow fields significantly.To develop an efficient flow field reconstruction model for this,we present an Improved Conditional Denoising Diffusion Generative Adversarial Network(ICDDGAN),which integrates Conditional Denoising Diffusion Probabilistic Models(CDDPMs)with Style GAN,and introduce a reconstruction discrimination mechanism and dynamic loss weight learning strategy.We establish the Mach number flow field dataset by numerical simulation at various backpressures for the mode transition process from turbine mode to ejector ramjet mode at Mach number 2.5.The proposed ICDDGAN model,given only sparse parameter information,can rapidly generate high-quality Mach number flow fields without a large number of samples for training.The results show that ICDDGAN is superior to CDDGAN in terms of training convergence and stability.Moreover,the interpolation and extrapolation test results during backpressure conditions show that ICDDGAN can accurately and quickly reconstruct Mach number fields at various tunnel slice shapes,with a Structural Similarity Index Measure(SSIM)of over 0.96 and a Mean-Square Error(MSE)of 0.035%to actual flow fields,reducing time costs by 7-8 orders of magnitude compared to Computational Fluid Dynamics(CFD)calculations.This can provide an efficient means for rapid computation of complex flow fields.
文摘County economies form a distinctive,integrated regional economic structure.Their growth is shaped by specific social and historical conditions and,in turn,influences many aspects of wider economic and social development.In China's modernization process,they have always played a vital role.The 2024 Central Economic Work Conference placed strong emphasis on vigorously developing county economies.
基金Chongqing Light Alloy Materials and Processing Engineering Technology Research Center Open Fund Project(GCZX201903)Yunnan Province Major Science and Technology Special Project Plan(202302AA310038)Sichuan University-Suining Municipal-University Cooperation Project(2023CDSN-12)。
文摘Ti(C,N)-Mo_(2)C-Ni cermet as alternative materials was explored for use in alkaline conditions,replacing the WC-Co cemented carbides,since Co is classified as a potentially carcinogenic substance and there is potential hazard of“hard metal disease”under the exposure to cobalt dust.The changes in microstructure,corrosion rate and volumetric loss rate of the two materials were compared under electrochemical corrosion and erosion-corrosion in alkaline environment.The results demonstrates that Ti(C,N)-Mo_(2)C-Ni cermet undergoes passivation when exposed to electrochemical corrosion of NaOH solution,resulting in a significant increase in oxygen content on the corroded surface.The corrosion rate of cermet is approximately one order of magnitude lower than that of the cemented carbide.Under the erosion-corrosion of an alkaline sand-water mixture,both the cermet and cemented carbide experience a gradual increase in volumetric loss rate with prolonging the erosion time.During erosion,the rim phase in cermet is fragile,so cracks easily penetrate it while the core phase remains intact.The medium-grained cemented carbide commonly demonstrates transgranular fracture mode,while in the fine-grained cemented carbide,cracks tend to propagate along phase boundaries.The erosive wear and damage caused by sand particles play a predominant role in the erosion-corrosion process of alkaline sand-water mixtures.This process represents an accelerated destructive phenomenon influenced and intensified by the combined effects of corrosion and erosion.It is confirmed that using cermet as an alternative anti-wear material to cemented carbides is feasible under alkaline conditions,and even better.
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
基金support by the National Natural Science Foundation of China(Grant No.52402520)。
文摘Actuator faults can be critical in turbofan engines as they can lead to stall,surge,loss of thrust and failure of speed control.Thus,fault diagnosis of gas turbine actuators has attracted considerable attention,from both academia and industry.However,the extensive literature that exists on this topic does not address identifying the severity of actuator faults and focuses mainly on actuator fault detection and isolation.In addition,previous studies of actuator fault identification have not dealt with multiple concurrent faults in real time,especially when these are accompanied by sudden failures under dynamic conditions.This study develops component-level models for fault identification in four typical actuators used in high-bypass ratio turbofan engines under both dynamic and steady-state conditions and these are then integrated with the engine performance model developed by the authors.The research results reported here present a novel method of quantifying actuator faults using dynamic effect compensation.The maximum error for each actuator is less than0.06%and 0.07%,with average computational time of less than 0.0058 s and 0.0086 s for steady-state and transient cases,respectively.These results confirm that the proposed method can accurately and efficiently identify concurrent actuator fault for an engine operating under either transient or steady-state conditions,even in the case of a sudden malfunction.The research results emonstrate the potential benefit to emergency response capabilities by introducing this method of monitoring the health of aero engines.
基金funding support from the National Natural Science Foundation of China(Grant No.12172019).
文摘In cold regions,rock structures will be weakened by freeze-thaw cycles under various water immersion conditions.Determining how water immersion conditions impact rock deterioration under freeze-thaw cycles is critical to assess accurately the frost resistance of engineered rock.In this paper,freeze-thaw cycles(temperature range of-20℃-20℃)were performed on the sandstones in different water immersion conditions(fully,partially and non-immersed in water).Then,computed tomography(CT)tests were conducted on the sandstones when the freeze-thaw number reached 0,5,10,15,20 and 30.Next,the effects of water immersion conditions on the microstructure deterioration of sandstone under freezethaw cycles were evaluated using CT spatial imaging,porosity and damage factor.Finally,focusing on the partially immersed condition,the immersion volume rate was defined to understand the effects of immersion degree on the freeze-thaw damage of sandstone and to propose a damage model considering the freeze-thaw number and immersion degree.The results show that with increasing freeze-thaw number,the porosities and damage factors under fully and partially immersed conditions increase continuously,while those under non-immersed condition first increase and then remain approximately constant.The most severe freeze-thaw damage occurs in fully immersed condition,followed by partially immersed condition and finally non-immersed condition.Interestingly,the freeze-thaw number and the immersion volume rate both impact the microstructure deterioration of the partially immersed sandstone.For the same freeze-thaw number,the damage factor increases approximately linearly with increasing immersion volume rate,and the increasing immersion degree exacerbates the microstructure deterioration of sandstone.Moreover,the proposed model can effectively estimate the freeze-thaw damage of partially immersed sandstone with different immersion volume rates.
基金supported by the National Key Research and Development Program of China(No.2019YFC1803501)the National Natural Science Foundation of China(No.52074357)+2 种基金the Natural Science Foundation of Hunan Province,China(No.2022JJ30713)the Vanadium Titanium Union Foundationthe Project of Technology Innovation Center for Comprehensive Utilization of Strategic Mineral Resources,Ministry of Natural Resources,China。
文摘The potential of 2-amino-1-propanol(AP)as a novel depressant in selectively floating ilmenite from titanaugite under weakly acidic conditions was investigated.Micro-flotation results show that AP significantly reduces the recovery of titanaugite while having no evident impact on ilmenite flotation.Subsequent bench-scale flotation tests further confirm a remarkable improvement in separation efficiency upon the introduction of AP.Contact angle and adsorption tests reveal a stronger affinity of AP towards the titanaugite surface in comparison to ilmenite.Zeta potential measurements and X-ray photoelectron spectroscopy(XPS)analyses exhibit favorable adsorption characteristics of AP on titanaugite,resulting from a synergy of electrostatic attraction and chemical interaction.In contrast,electrostatic repulsion hinders any significant interaction between AP and the ilmenite surface.These findings highlight the potential of AP as a highly efficient depressant for ilmenite flotation,paving the way for reduced reliance on sulfuric acid in the industry.
基金funded by the Natural Science Foundation of China(Grant Nos.42377164 and 41972280)the Badong National Observation and Research Station of Geohazards(Grant No.BNORSG-202305).
文摘Landslide susceptibility prediction(LSP)is significantly affected by the uncertainty issue of landslide related conditioning factor selection.However,most of literature only performs comparative studies on a certain conditioning factor selection method rather than systematically study this uncertainty issue.Targeted,this study aims to systematically explore the influence rules of various commonly used conditioning factor selection methods on LSP,and on this basis to innovatively propose a principle with universal application for optimal selection of conditioning factors.An'yuan County in southern China is taken as example considering 431 landslides and 29 types of conditioning factors.Five commonly used factor selection methods,namely,the correlation analysis(CA),linear regression(LR),principal component analysis(PCA),rough set(RS)and artificial neural network(ANN),are applied to select the optimal factor combinations from the original 29 conditioning factors.The factor selection results are then used as inputs of four types of common machine learning models to construct 20 types of combined models,such as CA-multilayer perceptron,CA-random forest.Additionally,multifactor-based multilayer perceptron random forest models that selecting conditioning factors based on the proposed principle of“accurate data,rich types,clear significance,feasible operation and avoiding duplication”are constructed for comparisons.Finally,the LSP uncertainties are evaluated by the accuracy,susceptibility index distribution,etc.Results show that:(1)multifactor-based models have generally higher LSP performance and lower uncertainties than those of factors selection-based models;(2)Influence degree of different machine learning on LSP accuracy is greater than that of different factor selection methods.Conclusively,the above commonly used conditioning factor selection methods are not ideal for improving LSP performance and may complicate the LSP processes.In contrast,a satisfied combination of conditioning factors can be constructed according to the proposed principle.
