Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance...Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance in ovarian cancer is not well characterized.This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer,particularly in relation to cisplatin resistance.Methods:The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR,immunofluorescence staining,immunohistochemistry,and western blotting.Prognostic associations were conducted using the Kaplan-Meier Plotter database.Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity.Ferroptosis-related parameters,including intracellular iron content,glutathione(GSH)levels,reactive oxygen species(ROS)generation,and mitochondrial membrane potential,were measured to determine ferroptotic changes.In vivo experiments were carried out to determine the antitumor efficacy of RPS6KA2 modulation in combination with pathway-specific agents.Results:Using ovarian cancer cell lines and clinical tissue samples,we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts.Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance.Mechanistically,RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)signaling pathway,which in turn increased sensitivity to cisplatin.Additionally,RPS6KA2 facilitated ferroptosis,contributing to its tumor-suppressive function.miR-512-3p was identified as a negative regulator of RPS6KA2,driving cisplatin resistance through suppression of RPS6KA2 expression.In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models.Conclusion:These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.展开更多
A comprehensive full-sieve-hole grading correction method was used to adjust aggregate gradings.The fatigue properties of recycled concrete aggregate(RCA)asphalt mixtures were investigated using an improved indirect t...A comprehensive full-sieve-hole grading correction method was used to adjust aggregate gradings.The fatigue properties of recycled concrete aggregate(RCA)asphalt mixtures were investigated using an improved indirect tensile fatigue test under temperature-humidity coupling based on 20-year meteorological data of Beijing,and the degeneration mechanism was further explored by scanning electron microscopy and energy-dispersive spectroscopy.The experimental results indicate that replacing 5-20 mm coarse limestone aggregate(LA)with RCA at a 50% substitution volume can mitigate the impact of RCA variations on the asphalt mixture proportioning design.All RCA asphalt mixtures have lower initial fatigue properties than the LA asphalt mixture.However,under temperature-humidity coupling,the long-term fatigue property of an RCA asphalt mixture with a low proportion of recycled brick exceeds that of the LA asphalt mixture,and the fatigue life decline rate of the RCA asphalt mixture during 10-year service decreases by approximately 25%.This is due to the penetration of the asphalt mortar into the RCA through the pores and cracks on the RCA surface.It forms an interfacial transition zone composed of asphalt mortar and cement mortar and further reduces the mixture damage caused by the water and freeze-thaw conditions.展开更多
Pre-chamber ignition technology can address the issue of uneven in-cylinder mixture combustion in large-bore marine engines.The impact of various pre-chamber structures on the formation of the mixture and jet flames w...Pre-chamber ignition technology can address the issue of uneven in-cylinder mixture combustion in large-bore marine engines.The impact of various pre-chamber structures on the formation of the mixture and jet flames within the pre-chamber is explored.This study performed numerical simulations on a large-bore marine ammonia/hydrogen pre-chamber engine prototype,considering pre-chamber volume,throat diameter,the distance between the hydrogen injector and the spark plug,and the hydrogen injector angle.Compared with the original engine,when the pre-chamber volume is 73.4 ml,the throat diameter is 14 mm,the distance ratio is 0.92,and the hydrogen injector angle is 80°.Moreover,the peak pressure in the pre-chamber increased by 23.1%,and that in the main chamber increased by 46.3%.The results indicate that the performance of the original engine is greatly enhanced by altering its fuel and pre-chamber structure.展开更多
In recent years,the amount of waste generated during milling has increased dramatically,and improper disposal poses a significant environmental challenge.To mitigate environmental pollution and enhance the road perfor...In recent years,the amount of waste generated during milling has increased dramatically,and improper disposal poses a significant environmental challenge.To mitigate environmental pollution and enhance the road performance of emulsified asphalt cold recycled mixtures(ECRM),this study employed recycled asphalt pavement(RAP)and reclaimed inorganic binder stabilized aggregate(RAI)as dual recycled materials for ECRM preparation.The blending ratios of reclaimed base and surface layer mixtures significantly influence ECRM's performance,with adjusted proportions substantially improving compressive strength and dynamic modulus.Firstly,three distinct proportioning options were developed for the recycled materials.Mix designs incorporating varying RAP/RAI ratios were used to determine the optimal mix parameters:moisture content,cement dosage,and emulsified asphalt content.Subsequently,comprehensive performance evaluations were conducted through high-temperature wheel tracking tests,freeze-thaw splitting tests,uniaxial compression tests,and dynamic modulus measurements to analyze the pavement characteristics of the three ECRM formulations.Experimental results demonstrate:Compared with ECRM with a blending ratio of RAP:RAI:new aggregate=30:50:20(Option 1),the dynamic stability,freeze-thaw splitting strength ratio,compressive strength,and compressive resilient modulus of ECRM under Option 3(RAP:RAI:new aggregate=50:30:20)decreased by 31.8%,5.2%,16.4%,and 13.1%,respectively.This indicates that increasing RAP content while reducing RAI proportion enhances the tensile strength of ECRM,yet adversely affects its high-temperature stability,moisture resistance,and compressive performance.This work not only addresses the challenge of jointly utilizing asphalt pavement waste and base waste,but also provides a cost-effective and sustainable method for the stable application of milling material resources in road engineering.展开更多
BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recogn...BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recognized in family-centered clinical practice.Concurrently,against the backdrop of rising rates of delayed marriage and China’s Maternity Incentive Policy,the proportion of women giving birth at an advanced maternal age is increasing.Nevertheless,research specifically examining PPD among spouses of older mothers remains critically scarce,both in China and globally.AIM To investigate PPD and its influencing factors in Chinese advanced maternal age families.METHODS This cross-sectional study included 358 participants;it was conducted among fathers of pregnant women of advanced maternal age at five hospitals in the Pearl River Delta region of China from September 2023 to June 2024.Data were collected via a general information questionnaire,the Social Support Rating Scale,and the Edinburgh Postnatal Depression Scale.Latent profile analysis and regression mixture models(RMMs)were adopted to analyze the latent PPD types and factors that influenced PPD.RESULTS The incidence of PPD was 16.48%,and three profiles were identified:Low-symptomatic(175 cases,48.89%),monophasic(140 cases,39.10%),and high-symptomatic(43 cases,12.01%).The RMM analysis revealed that first pregnancy,low income(<¥3000/month),part-time work,and a history of abnormal pregnancy were positively associated with the high-symptomatic type(P<0.05).Conversely,high subjective support and support utilization were negatively associated with the high-symptomatic type compared with the low-symptomatic type(P<0.05).Good couple relationships,high objective and subjective support,and high support utilization were negatively associated with monophasic disorder(P<0.05).CONCLUSION PPD incidence is high among Chinese fathers with advanced maternal age partners,and the characteristics of depression are varied.Healthcare practitioners should prioritize individuals with low levels of social support.展开更多
In this paper,a prediction model is developed that combines a Gaussian mixture model(GMM) and a Kalman filter for online forecasting of traffic safety on expressways.Raw time-to-collision(TTC) samples are divided into...In this paper,a prediction model is developed that combines a Gaussian mixture model(GMM) and a Kalman filter for online forecasting of traffic safety on expressways.Raw time-to-collision(TTC) samples are divided into two categories:those representing vehicles in risky situations and those in safe situations.Then,the GMM is used to model the bimodal distribution of the TTC samples,and the maximum likelihood(ML) estimation parameters of the TTC distribution are obtained using the expectation-maximization(EM) algorithm.We propose a new traffic safety indicator,named the proportion of exposure to traffic conflicts(PETTC),for assessing the risk and predicting the safety of expressway traffic.A Kalman filter is applied to forecast the short-term safety indicator,PETTC,and solves the online safety prediction problem.A dataset collected from four different expressway locations is used for performance estimation.The test results demonstrate the precision and robustness of the prediction model under different traffic conditions and using different datasets.These results could help decision-makers to improve their online traffic safety forecasting and enable the optimal operation of expressway traffic management systems.展开更多
The mechanism for development of littoral karst differs from that of inland karst, and the mixture corrosion effects are one of the most important factors that control the development of littoral karst. Through seven ...The mechanism for development of littoral karst differs from that of inland karst, and the mixture corrosion effects are one of the most important factors that control the development of littoral karst. Through seven groups of static experiments carried out in a closed CO2-H2O system, basic conclusions can be drawn as follows: (1) the basic law of corrosion process in a transitional zone of seawater-freshwater in littoral karst areas is identical with that in the fresh water, i.e., the lithologic characteristics and rock structure are the main factors which control the development of littoral karst; (2) the mixture corrosion rate of the carbonate rock in the above transitional zone is faster than that in fresh water or seawater; (3) the mechanism for development of carbonate rocks differs at various pressures of CO2 in a transitional zone in littoral karst areas.展开更多
基金supported by the Academic Leader Training Programof Pudong New Area Health System in Shanghai(Grant No.PWRd2021-13)Shanghai Municipal Health Commission(Grant No.202340094).
文摘Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance in ovarian cancer is not well characterized.This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer,particularly in relation to cisplatin resistance.Methods:The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR,immunofluorescence staining,immunohistochemistry,and western blotting.Prognostic associations were conducted using the Kaplan-Meier Plotter database.Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity.Ferroptosis-related parameters,including intracellular iron content,glutathione(GSH)levels,reactive oxygen species(ROS)generation,and mitochondrial membrane potential,were measured to determine ferroptotic changes.In vivo experiments were carried out to determine the antitumor efficacy of RPS6KA2 modulation in combination with pathway-specific agents.Results:Using ovarian cancer cell lines and clinical tissue samples,we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts.Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance.Mechanistically,RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)signaling pathway,which in turn increased sensitivity to cisplatin.Additionally,RPS6KA2 facilitated ferroptosis,contributing to its tumor-suppressive function.miR-512-3p was identified as a negative regulator of RPS6KA2,driving cisplatin resistance through suppression of RPS6KA2 expression.In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models.Conclusion:These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.
基金Funded by"Green Construction and Maintenance of Road Engineering"the Belt and Road Joint Laboratory,International(Hong Kong,Macao and Taiwan)Science and Technology Cooperation Project(No.Z251100007125040)the National Key R&D Program of China(No.2022YFC3803403)+3 种基金the Project of Construction and Support for High-level Innovative Teams of Beijing Municipal Institutions(No.BPHR20220109)the Cultivation Project Funds for Beijing University of Civil Engineering and Architecture(No.X24013)the BUCEA Doctor Graduate Scientific Research Ability Improvement Project(No.DG2024016)the China Scholarship Council(No.202408110091)。
文摘A comprehensive full-sieve-hole grading correction method was used to adjust aggregate gradings.The fatigue properties of recycled concrete aggregate(RCA)asphalt mixtures were investigated using an improved indirect tensile fatigue test under temperature-humidity coupling based on 20-year meteorological data of Beijing,and the degeneration mechanism was further explored by scanning electron microscopy and energy-dispersive spectroscopy.The experimental results indicate that replacing 5-20 mm coarse limestone aggregate(LA)with RCA at a 50% substitution volume can mitigate the impact of RCA variations on the asphalt mixture proportioning design.All RCA asphalt mixtures have lower initial fatigue properties than the LA asphalt mixture.However,under temperature-humidity coupling,the long-term fatigue property of an RCA asphalt mixture with a low proportion of recycled brick exceeds that of the LA asphalt mixture,and the fatigue life decline rate of the RCA asphalt mixture during 10-year service decreases by approximately 25%.This is due to the penetration of the asphalt mortar into the RCA through the pores and cracks on the RCA surface.It forms an interfacial transition zone composed of asphalt mortar and cement mortar and further reduces the mixture damage caused by the water and freeze-thaw conditions.
基金Supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions under Grant No.014000319/2018-00391.
文摘Pre-chamber ignition technology can address the issue of uneven in-cylinder mixture combustion in large-bore marine engines.The impact of various pre-chamber structures on the formation of the mixture and jet flames within the pre-chamber is explored.This study performed numerical simulations on a large-bore marine ammonia/hydrogen pre-chamber engine prototype,considering pre-chamber volume,throat diameter,the distance between the hydrogen injector and the spark plug,and the hydrogen injector angle.Compared with the original engine,when the pre-chamber volume is 73.4 ml,the throat diameter is 14 mm,the distance ratio is 0.92,and the hydrogen injector angle is 80°.Moreover,the peak pressure in the pre-chamber increased by 23.1%,and that in the main chamber increased by 46.3%.The results indicate that the performance of the original engine is greatly enhanced by altering its fuel and pre-chamber structure.
基金sponsored by National Natural Science Foundation of China(No.52308466)SASAC Science and Technology Innovation Project(JF-23-01-0063)Shaanxi Provincial Transportation Research Project(25-84 K,25-85 K).
文摘In recent years,the amount of waste generated during milling has increased dramatically,and improper disposal poses a significant environmental challenge.To mitigate environmental pollution and enhance the road performance of emulsified asphalt cold recycled mixtures(ECRM),this study employed recycled asphalt pavement(RAP)and reclaimed inorganic binder stabilized aggregate(RAI)as dual recycled materials for ECRM preparation.The blending ratios of reclaimed base and surface layer mixtures significantly influence ECRM's performance,with adjusted proportions substantially improving compressive strength and dynamic modulus.Firstly,three distinct proportioning options were developed for the recycled materials.Mix designs incorporating varying RAP/RAI ratios were used to determine the optimal mix parameters:moisture content,cement dosage,and emulsified asphalt content.Subsequently,comprehensive performance evaluations were conducted through high-temperature wheel tracking tests,freeze-thaw splitting tests,uniaxial compression tests,and dynamic modulus measurements to analyze the pavement characteristics of the three ECRM formulations.Experimental results demonstrate:Compared with ECRM with a blending ratio of RAP:RAI:new aggregate=30:50:20(Option 1),the dynamic stability,freeze-thaw splitting strength ratio,compressive strength,and compressive resilient modulus of ECRM under Option 3(RAP:RAI:new aggregate=50:30:20)decreased by 31.8%,5.2%,16.4%,and 13.1%,respectively.This indicates that increasing RAP content while reducing RAI proportion enhances the tensile strength of ECRM,yet adversely affects its high-temperature stability,moisture resistance,and compressive performance.This work not only addresses the challenge of jointly utilizing asphalt pavement waste and base waste,but also provides a cost-effective and sustainable method for the stable application of milling material resources in road engineering.
基金Supported by High-level Professional Groups in Gangdong Province,No.GSPZYQ2020101Guangdong Province Educational Research Planning Project,No.2024GXJK742。
文摘BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recognized in family-centered clinical practice.Concurrently,against the backdrop of rising rates of delayed marriage and China’s Maternity Incentive Policy,the proportion of women giving birth at an advanced maternal age is increasing.Nevertheless,research specifically examining PPD among spouses of older mothers remains critically scarce,both in China and globally.AIM To investigate PPD and its influencing factors in Chinese advanced maternal age families.METHODS This cross-sectional study included 358 participants;it was conducted among fathers of pregnant women of advanced maternal age at five hospitals in the Pearl River Delta region of China from September 2023 to June 2024.Data were collected via a general information questionnaire,the Social Support Rating Scale,and the Edinburgh Postnatal Depression Scale.Latent profile analysis and regression mixture models(RMMs)were adopted to analyze the latent PPD types and factors that influenced PPD.RESULTS The incidence of PPD was 16.48%,and three profiles were identified:Low-symptomatic(175 cases,48.89%),monophasic(140 cases,39.10%),and high-symptomatic(43 cases,12.01%).The RMM analysis revealed that first pregnancy,low income(<¥3000/month),part-time work,and a history of abnormal pregnancy were positively associated with the high-symptomatic type(P<0.05).Conversely,high subjective support and support utilization were negatively associated with the high-symptomatic type compared with the low-symptomatic type(P<0.05).Good couple relationships,high objective and subjective support,and high support utilization were negatively associated with monophasic disorder(P<0.05).CONCLUSION PPD incidence is high among Chinese fathers with advanced maternal age partners,and the characteristics of depression are varied.Healthcare practitioners should prioritize individuals with low levels of social support.
基金Project (No. 2011AA110304) supported by the National High-Tech R&D Program of China (863 program)
文摘In this paper,a prediction model is developed that combines a Gaussian mixture model(GMM) and a Kalman filter for online forecasting of traffic safety on expressways.Raw time-to-collision(TTC) samples are divided into two categories:those representing vehicles in risky situations and those in safe situations.Then,the GMM is used to model the bimodal distribution of the TTC samples,and the maximum likelihood(ML) estimation parameters of the TTC distribution are obtained using the expectation-maximization(EM) algorithm.We propose a new traffic safety indicator,named the proportion of exposure to traffic conflicts(PETTC),for assessing the risk and predicting the safety of expressway traffic.A Kalman filter is applied to forecast the short-term safety indicator,PETTC,and solves the online safety prediction problem.A dataset collected from four different expressway locations is used for performance estimation.The test results demonstrate the precision and robustness of the prediction model under different traffic conditions and using different datasets.These results could help decision-makers to improve their online traffic safety forecasting and enable the optimal operation of expressway traffic management systems.
基金supported by the National Natural Science Foundation of China(grant 49832005)IGCP443 Magnesite and Talc Geological and Environmental Correlations.
文摘The mechanism for development of littoral karst differs from that of inland karst, and the mixture corrosion effects are one of the most important factors that control the development of littoral karst. Through seven groups of static experiments carried out in a closed CO2-H2O system, basic conclusions can be drawn as follows: (1) the basic law of corrosion process in a transitional zone of seawater-freshwater in littoral karst areas is identical with that in the fresh water, i.e., the lithologic characteristics and rock structure are the main factors which control the development of littoral karst; (2) the mixture corrosion rate of the carbonate rock in the above transitional zone is faster than that in fresh water or seawater; (3) the mechanism for development of carbonate rocks differs at various pressures of CO2 in a transitional zone in littoral karst areas.
