Four-Wheel Independent Steering(4WIS)Vehicles can independently control the angle of each wheel,demonstrating superior trajectory tracking performance under normal conditions.However,on intermittent icy and snowy road...Four-Wheel Independent Steering(4WIS)Vehicles can independently control the angle of each wheel,demonstrating superior trajectory tracking performance under normal conditions.However,on intermittent icy and snowy roads,the presence of time-varying adhesion coefficients,time-varying cornering stiffness,and the irregularities due to ice and snow accumulation introduce multiple uncertainties into the steering system,significantly degrading the trajectory tracking performance of 4WIS vehicles.In response,this paper proposes a robust Tube Model Predictive Control(Tube-MPC)trajectory tracking control method for 4WIS.In this method,a Bi-directional Long Short-Term Memory neural network is established for online estimation of tire cornering stiffness under different road adhesion coefficients,providing accurate estimation of time-varying cornering stiffness for each wheel to mitigate the uncertainties of time-varying adhesion coefficients and cornering stiffness.Additionally,considering the road irregularities caused by snow accumulation on intermittent icy and snowy roads,a trajectory tracking controller that integrates Tube-MPC and robust Sliding Mode Control is proposed.The nominal MPC model,developed from the estimated tire cornering stiffness,utilizes the sliding surface and the optimal auxiliary control unit law for the tube is derived from the reaching law in Tube-MPC,aiming to minimize the trajectory tracking error while enhancing the controller’s robustness against road uncertainties.The experiments show that the proposed method outperforms the Tube-MPC algorithm in terms of trajectory accuracy and robustness.This method demonstrates excellent trajectory tracking accuracy under intermittent icy and snowy road conditions,and it lays a theoretical foundation for future studies on vehicle stability and trajectory tracking under such road conditions.展开更多
目的:利用iCys激光定量成像细胞仪(iCys research imaging cytometer,RIC)对小鼠全心脏切片中标记的化学发光或荧光信号进行大面积、高速度、高分辨率的扫描,根据所获得图像统计分析小鼠全心脏切片中荧光和化学发光的阳性细胞比例,并分...目的:利用iCys激光定量成像细胞仪(iCys research imaging cytometer,RIC)对小鼠全心脏切片中标记的化学发光或荧光信号进行大面积、高速度、高分辨率的扫描,根据所获得图像统计分析小鼠全心脏切片中荧光和化学发光的阳性细胞比例,并分群追踪分析对象的图像以排查假阳性。方法:利用血管紧张素II灌注小鼠,对心脏切片进行巨噬细胞特异性的mac-2抗体的免疫组化,通过光电二极管(photodiode,PD)检测器收集二氨基联苯胺法(DAB染色法)的化学发光信号获得全心脏相关影像,进而分析图片以统计全心脏中的巨噬细胞的阳性面积;利用小鼠心肌梗塞模型后心脏进行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling,TUNEL)标记,通过器光电倍增管(photo multiplier tube,PMT)检测器收集荧光信号获得全心脏相关影像,进而分析图片以统计全心脏中的细胞死亡率。结果:400倍放大时iCys激光定量成像细胞仪对小鼠全心脏切片的扫描花费大约20min,获得大约300张局部图片,软件自动拼合成全心脏切片图。通过对全心脏图片的统计分析显示:AngII灌注的全心脏中DAB染色法显示的mac-2抗体阳性巨噬细胞阳性面积为(2.36±0.7)%;全心脏的TUNEL标记后荧光阳性的死亡细胞比率为(32.3±4.1)%。结论:iCys激光定量成像细胞仪可以对病理切片样本中的化学发光以及荧光信号进行大面积、高速度、高清晰的扫描,分析软件可以进行后期的图像的定性定量分析,并且可以通过对分析对象的追踪图像显示以明确统计分析的正确性。展开更多
Based on the daily mean temperature and 24-h accumulated total precipitation over central and southern China, the features and the possible causes of the extreme weather events with low temperature and icing condition...Based on the daily mean temperature and 24-h accumulated total precipitation over central and southern China, the features and the possible causes of the extreme weather events with low temperature and icing conditions,which occurred in the southern part of China during early 2008, are investigated in this study. In addition, multimodel consensus forecasting experiments are conducted by using the ensemble forecasts of ECMWF, JMA, NCEP and CMA taken from the TIGGE archives. Results show that more than a third of the stations in the southern part of China were covered by the extremely abundant precipitation with a 50-a return period, and extremely low temperature with a 50-a return period occurred in the Guizhou and western Hunan province as well. For the 24- to 216-h surface temperature forecasts, the bias-removed multimodel ensemble mean with running training period(R-BREM) has the highest forecast skill of all individual models and multimodel consensus techniques. Taking the RMSEs of the ECMWF 96-h forecasts as the criterion, the forecast time of the surface temperature may be prolonged to 192 h over the southeastern coast of China by using the R-BREM technique. For the sprinkle forecasts over central and southern China, the R-BREM technique has the best performance in terms of threat scores(TS) for the 24- to 192-h forecasts except for the 72-h forecasts among all individual models and multimodel consensus techniques. For the moderate rain, the forecast skill of the R-BREM technique is superior to those of individual models and multimodel ensemble mean.展开更多
The anti-skid performance of snowy and icy pavements is a popular research topic among road workers.Snow and ice are pollutants on a road surface.They significantly reduce the skid resistance of pavements,and thus,cau...The anti-skid performance of snowy and icy pavements is a popular research topic among road workers.Snow and ice are pollutants on a road surface.They significantly reduce the skid resistance of pavements,and thus,cause traffic accidents.Pertinent research progress on the skid resistance of snowy and icy pavements was reviewed and summarized in this work.The formation and classification of snowy and icy pavements were described on the basis of the state of snow and ice.The friction mechanisms between tires and snowy and icy pavements were revealed.Measurement methods and their applicability to the skid resistance of snowy and icy pavements were summarized.Factors that affect the skid resistance of pavements were discussed from the perspectives of pavement,environment,and vehicle.In addition,models of snowy and icy pavement resistance were classified into experience,mechanical,and numerical models.The advantages and disadvantages of these models were then compared and analyzed.Some suggestions regarding snowy and icy pavements were presented in accordance with the aforementioned information,including the development of efficient testing tools,the quantification of skid resistance under the coupling effects of multiple factors,the establishment of unified evaluation standards,and the development of more effective skid resistance models.展开更多
Low temperature together with snow/freezing rain is disastrous in winter over southern China.Previous studies suggest that this is related to the sea surface temperature(SST)anomalies,especially La Nina conditions,ove...Low temperature together with snow/freezing rain is disastrous in winter over southern China.Previous studies suggest that this is related to the sea surface temperature(SST)anomalies,especially La Nina conditions,over the equatorial central–eastern Pacific Ocean(EP).In reality,however,La Nina episodes are not always accompanied by rainy/snowy/icy(CRSI)days in southern China,such as the case in winter 2020/2021.Is there any other factor that works jointly with the EP SST to affect the winter CRSI weather in southern China?To address this question,CRSI days are defined and calculated based on station observation data,and the related SST anomalies and atmospheric circulations are examined based on the Hadley Centre SST data and the NCEP/NCAR reanalysis data for winters of1978/1979–2017/2018.The results indicate that the CRSI weather with more CRSI days is featured with both decreased temperature and increased winter precipitation over southern China.The SSTs over both the EP and the southeastern Indian Ocean(SIO)are closely related to the CRSI days in southern China with correlation coefficients of-0.29 and 0.39,significant at the 90%and 95%confidence levels,respectively.The SST over EP affects significantly air temperature,as revealed by previous studies,with cooler EP closely related to the deepened East Asian trough,which benefits stronger East Asian winter monsoon(EAWM)and lower air temperature in southern China.Nevertheless,this paper discovers that the SST over SIO affects precipitation of southern China,with a correlation coefficient of 0.42,significant at the 99%confidence level,with warmer SIO correlated with deepened southern branch trough(SBT)and strengthened western North Pacific anomalous anticyclone(WNPAC),favoring more water vapor convergence and enhanced precipitation in southern China.Given presence of La Ni?a in both winters,compared to the winter of 2020/2021,the winter of 2021/2022 witnessed more CRSI days,perhaps due to the warmer SIO.展开更多
In the solar system, Icy Worlds such as Europa and Enceladus hold great potential for extraterrestrial life and may provide humanity an answer, within this century, to the age-old question of life beyond Earth. Exo-AU...In the solar system, Icy Worlds such as Europa and Enceladus hold great potential for extraterrestrial life and may provide humanity an answer, within this century, to the age-old question of life beyond Earth. Exo-AUV technology shows promise in life detection in the icy shell, at the ice-water interface and on the seafloor of exo-ocean. Space agencies, including NASA and DLR, are enthusiastic about deploying Exo-AUVs to explore life in these regions. However, the where and how to find life, the technologies to be utilized and the goals to be achieved are crucial aspects for future Exo-AUV life detection missions on Icy Worlds. This study delves into a hypothetical mission of life detection on Europa, discussing science goals,detectable objects, potential regions and biogenic analysis for Icy Worlds. It proposes a life detection strategy for Icy Worlds based on Exo-AUVs, presents key contextual elements for Exo-AUV operations, outlines technological requirements for hull,payloads and autonomy, introduces the current state of Exo-AUV research and addresses existing challenges. This study also suggests a roadmap for conceptual development of Exo-AUV and a Concept of Operations for Multiple Exo-AUV System(ConOps for MEAS). This system aims to assist planetary scientists and astrobiologists in exploring Icy Worlds, identifying robust biosignatures and potentially discovering extant organisms, even prebiotic chemical systems.展开更多
Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
Profs.Yang Jun(杨军)and Hu Yongyun(胡永云)at the Department of Atmospheric and Oceanic Sciences,School of Physics,Peking University,and their collaborators recently published a paper in Nature Geoscience(http://www.na...Profs.Yang Jun(杨军)and Hu Yongyun(胡永云)at the Department of Atmospheric and Oceanic Sciences,School of Physics,Peking University,and their collaborators recently published a paper in Nature Geoscience(http://www.nature.com/ngeo/journal/v10/n8/pdf/ngeo2994.pdf).They show展开更多
人类是孤独的,遥望夜空,星汉灿烂!然而,茫茫宇宙,只有地球,是一个生机勃勃、各种生命繁衍不息的星球。Jupiter(木星)有一颗卫星,叫Europa(木卫二),其体积与地球相仿。从Galileo spacecraft传回的信息发现:the presence of water in liqu...人类是孤独的,遥望夜空,星汉灿烂!然而,茫茫宇宙,只有地球,是一个生机勃勃、各种生命繁衍不息的星球。Jupiter(木星)有一颗卫星,叫Europa(木卫二),其体积与地球相仿。从Galileo spacecraft传回的信息发现:the presence of water in liquid form on Europa。虽然。科学家们尚不明白whether the water was frozen or in liquid form,但是,他们已经展开了想象的双翅: Even though it is buried beneath a thick layer of ice, life forms could draw energy from heat sources below, just asdeep-sea creatures do in the Earth's oceans. 除了驰骋想象之外,美国国家航空和航天局在“囊中羞涩”之时,仍然决定:to send another spacecraft there!】展开更多
SUMMARIES OF TOP NEWS STORIES 42nd Antarctic Expedition Kicked Off China’s 42nd Antarctic expedition team set sail from Shanghai on 1 November.During this expedition,a suite of new technologies will be deployed and t...SUMMARIES OF TOP NEWS STORIES 42nd Antarctic Expedition Kicked Off China’s 42nd Antarctic expedition team set sail from Shanghai on 1 November.During this expedition,a suite of new technologies will be deployed and tested in the icy wilderness of the Antarctic.展开更多
Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunoth...Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes.展开更多
目的:本研究目的旨在探讨抗PD-1/PD-L1 (程序性细胞死亡蛋白-1,Programmed cell death-1/程序性死亡配体-1,Programmed death-ligand 1)治疗后发生心血管毒性死亡的风险因素,并以此构建预测模型。方法:本研究为单中心回顾性研究,通过系...目的:本研究目的旨在探讨抗PD-1/PD-L1 (程序性细胞死亡蛋白-1,Programmed cell death-1/程序性死亡配体-1,Programmed death-ligand 1)治疗后发生心血管毒性死亡的风险因素,并以此构建预测模型。方法:本研究为单中心回顾性研究,通过系统性回顾方法筛选2018年10月至2023年10月在青岛大学附属医院接受抗PD-1/PD-L1免疫治疗后的2665例实体肿瘤患者的病例资料观察180天,其中发生心血管毒性的33例,根据是否发生抗PD-1/PD-L1治疗心血管毒性死亡为结局,以是否发生死亡分为死亡组和存活组。采用单因素Cox回归分析其风险因素并控制相关混杂因素后构建预测模型绘制列线图。最后,利用受试者工作特征曲线(Receiver Operating Characteristic, ROC)、决策曲线分析法(Decision Curve Analysis, DCA)、校准曲线(Calibration Curve, CC)进行内部评价和内部验证。结果:1) 淋巴细胞计数、单核细胞计数、血小板计数、合并糖尿病、免疫检查点抑制剂种类、彩超室壁运动异常在心血管毒性存活组和死亡组间的差异均有统计学意义(均p Purpose: This study aimed to investigate risk factors for death from cardiovascular toxicity following anti-PD-1/PD-L1 therapy and develop a predictive model. Methods: This study was a single-center retrospective study, which screened the case data of 2665 patients with solid tumors after receiving anti-PD-1/PD-L1 immunotherapy at the Affiliated Hospital of Qingdao University for 180 days of observation by a systematic retrospective method, 33 cases of cardiovascular toxicity, and the outcome was based on whether or not death from cardiovascular toxicity of anti-PD-1/PD-L1 therapy occurred as the outcome categorized into death and survival groups. A one-way Cox regression analysis was used to analyze the risk factors and control for relevant confounders, and a predictive model was constructed to draw a column-line graph. Finally, Receiver Operating Characteristic (ROC), Decision Curve Analysis (DCA), and Calibration Curve (CC) were used for internal evaluation and internal validation. Results: 1) Lymphocyte, Platelet, Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte differences between two groups: those with death from cardiovascular toxicity and those without were statistically significant (all p < 0.05). 2) Univariate Cox regression identified diabetes (HR = 6.03, 95% CI 1.67~21.77, p = 0.006), Types of immune checkpoint inhibitors (HR = 6.62, 95% CI 1.69~25.89, p = 0.007), Echocardiographic ventricular wall motion abnormalities (HR = 4.61, 95% CI 1.19~17.85, p = 0.027), monocyte HR = 0.02, 95% CI 0.00~0.49, p = 0.015) as significant predictors. 3) Multivariate analysis confirmed monocyte (HR = 0.02, 95% CI 0.00~0.77, p = 0.036) as an independent predictor. 4) A predictive model for the risk of death from cardiovascular toxicity was constructed by including 4 variables (p < 0.05) from univariate Cox regression in a nomogram, with an AUC of 0.88 and 95% CI of 0.75 to 1.00. Conclusion: 1) Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte were significant predictors of death from cardiovascular toxicity. 2) Monocyte was an independent protective factor, after adjusting for other covariates. 3) A predictive model for the risk of cardiovascular toxic death was constructed by incorporating 4 variables from univariate Cox regression into a nomogram, and this model had good precision, discrimination, accuracy, and clinical benefit effects.展开更多
基金Supported by National Natural Science Foundation of China(Grant Nos.52405112,U24A20199)the Postdoctoral Fellowship Program of CPSF(Grant No.GZB20240973).
文摘Four-Wheel Independent Steering(4WIS)Vehicles can independently control the angle of each wheel,demonstrating superior trajectory tracking performance under normal conditions.However,on intermittent icy and snowy roads,the presence of time-varying adhesion coefficients,time-varying cornering stiffness,and the irregularities due to ice and snow accumulation introduce multiple uncertainties into the steering system,significantly degrading the trajectory tracking performance of 4WIS vehicles.In response,this paper proposes a robust Tube Model Predictive Control(Tube-MPC)trajectory tracking control method for 4WIS.In this method,a Bi-directional Long Short-Term Memory neural network is established for online estimation of tire cornering stiffness under different road adhesion coefficients,providing accurate estimation of time-varying cornering stiffness for each wheel to mitigate the uncertainties of time-varying adhesion coefficients and cornering stiffness.Additionally,considering the road irregularities caused by snow accumulation on intermittent icy and snowy roads,a trajectory tracking controller that integrates Tube-MPC and robust Sliding Mode Control is proposed.The nominal MPC model,developed from the estimated tire cornering stiffness,utilizes the sliding surface and the optimal auxiliary control unit law for the tube is derived from the reaching law in Tube-MPC,aiming to minimize the trajectory tracking error while enhancing the controller’s robustness against road uncertainties.The experiments show that the proposed method outperforms the Tube-MPC algorithm in terms of trajectory accuracy and robustness.This method demonstrates excellent trajectory tracking accuracy under intermittent icy and snowy road conditions,and it lays a theoretical foundation for future studies on vehicle stability and trajectory tracking under such road conditions.
文摘目的:利用iCys激光定量成像细胞仪(iCys research imaging cytometer,RIC)对小鼠全心脏切片中标记的化学发光或荧光信号进行大面积、高速度、高分辨率的扫描,根据所获得图像统计分析小鼠全心脏切片中荧光和化学发光的阳性细胞比例,并分群追踪分析对象的图像以排查假阳性。方法:利用血管紧张素II灌注小鼠,对心脏切片进行巨噬细胞特异性的mac-2抗体的免疫组化,通过光电二极管(photodiode,PD)检测器收集二氨基联苯胺法(DAB染色法)的化学发光信号获得全心脏相关影像,进而分析图片以统计全心脏中的巨噬细胞的阳性面积;利用小鼠心肌梗塞模型后心脏进行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling,TUNEL)标记,通过器光电倍增管(photo multiplier tube,PMT)检测器收集荧光信号获得全心脏相关影像,进而分析图片以统计全心脏中的细胞死亡率。结果:400倍放大时iCys激光定量成像细胞仪对小鼠全心脏切片的扫描花费大约20min,获得大约300张局部图片,软件自动拼合成全心脏切片图。通过对全心脏图片的统计分析显示:AngII灌注的全心脏中DAB染色法显示的mac-2抗体阳性巨噬细胞阳性面积为(2.36±0.7)%;全心脏的TUNEL标记后荧光阳性的死亡细胞比率为(32.3±4.1)%。结论:iCys激光定量成像细胞仪可以对病理切片样本中的化学发光以及荧光信号进行大面积、高速度、高清晰的扫描,分析软件可以进行后期的图像的定性定量分析,并且可以通过对分析对象的追踪图像显示以明确统计分析的正确性。
基金Special Scientific Research Fund of Meteorological Public Welfare Industries of China(GYHY(QX)2007-6-1)National Nature Science Foundation of China(41305081)
文摘Based on the daily mean temperature and 24-h accumulated total precipitation over central and southern China, the features and the possible causes of the extreme weather events with low temperature and icing conditions,which occurred in the southern part of China during early 2008, are investigated in this study. In addition, multimodel consensus forecasting experiments are conducted by using the ensemble forecasts of ECMWF, JMA, NCEP and CMA taken from the TIGGE archives. Results show that more than a third of the stations in the southern part of China were covered by the extremely abundant precipitation with a 50-a return period, and extremely low temperature with a 50-a return period occurred in the Guizhou and western Hunan province as well. For the 24- to 216-h surface temperature forecasts, the bias-removed multimodel ensemble mean with running training period(R-BREM) has the highest forecast skill of all individual models and multimodel consensus techniques. Taking the RMSEs of the ECMWF 96-h forecasts as the criterion, the forecast time of the surface temperature may be prolonged to 192 h over the southeastern coast of China by using the R-BREM technique. For the sprinkle forecasts over central and southern China, the R-BREM technique has the best performance in terms of threat scores(TS) for the 24- to 192-h forecasts except for the 72-h forecasts among all individual models and multimodel consensus techniques. For the moderate rain, the forecast skill of the R-BREM technique is superior to those of individual models and multimodel ensemble mean.
基金This work was supported by the National Natural Science Foundation of China Joint Fund for Regional Innovation and Development(Grant No.U20A20315)Key Research Project of Heilongjiang Province(Grant No.2022ZXJ02A02)+1 种基金Key R&D Plan Program of Hebei Province(Grant No.20375405D)Science and Technology Project of Qinghai Province(Grant No.2021-QY-207).
文摘The anti-skid performance of snowy and icy pavements is a popular research topic among road workers.Snow and ice are pollutants on a road surface.They significantly reduce the skid resistance of pavements,and thus,cause traffic accidents.Pertinent research progress on the skid resistance of snowy and icy pavements was reviewed and summarized in this work.The formation and classification of snowy and icy pavements were described on the basis of the state of snow and ice.The friction mechanisms between tires and snowy and icy pavements were revealed.Measurement methods and their applicability to the skid resistance of snowy and icy pavements were summarized.Factors that affect the skid resistance of pavements were discussed from the perspectives of pavement,environment,and vehicle.In addition,models of snowy and icy pavement resistance were classified into experience,mechanical,and numerical models.The advantages and disadvantages of these models were then compared and analyzed.Some suggestions regarding snowy and icy pavements were presented in accordance with the aforementioned information,including the development of efficient testing tools,the quantification of skid resistance under the coupling effects of multiple factors,the establishment of unified evaluation standards,and the development of more effective skid resistance models.
基金Supported by the National Natural Science Foundation of China(42088101)Joint Open Project of KLME&CIC-FEMD,NUIST(KLME202212)。
文摘Low temperature together with snow/freezing rain is disastrous in winter over southern China.Previous studies suggest that this is related to the sea surface temperature(SST)anomalies,especially La Nina conditions,over the equatorial central–eastern Pacific Ocean(EP).In reality,however,La Nina episodes are not always accompanied by rainy/snowy/icy(CRSI)days in southern China,such as the case in winter 2020/2021.Is there any other factor that works jointly with the EP SST to affect the winter CRSI weather in southern China?To address this question,CRSI days are defined and calculated based on station observation data,and the related SST anomalies and atmospheric circulations are examined based on the Hadley Centre SST data and the NCEP/NCAR reanalysis data for winters of1978/1979–2017/2018.The results indicate that the CRSI weather with more CRSI days is featured with both decreased temperature and increased winter precipitation over southern China.The SSTs over both the EP and the southeastern Indian Ocean(SIO)are closely related to the CRSI days in southern China with correlation coefficients of-0.29 and 0.39,significant at the 90%and 95%confidence levels,respectively.The SST over EP affects significantly air temperature,as revealed by previous studies,with cooler EP closely related to the deepened East Asian trough,which benefits stronger East Asian winter monsoon(EAWM)and lower air temperature in southern China.Nevertheless,this paper discovers that the SST over SIO affects precipitation of southern China,with a correlation coefficient of 0.42,significant at the 99%confidence level,with warmer SIO correlated with deepened southern branch trough(SBT)and strengthened western North Pacific anomalous anticyclone(WNPAC),favoring more water vapor convergence and enhanced precipitation in southern China.Given presence of La Ni?a in both winters,compared to the winter of 2020/2021,the winter of 2021/2022 witnessed more CRSI days,perhaps due to the warmer SIO.
基金supported by the National Natural Science Foundation of China for Distinguished Young Scholars (Grant No. 52025111)the Key Projects of the National Natural Science Foundation of China (Grant No. 51939003)。
文摘In the solar system, Icy Worlds such as Europa and Enceladus hold great potential for extraterrestrial life and may provide humanity an answer, within this century, to the age-old question of life beyond Earth. Exo-AUV technology shows promise in life detection in the icy shell, at the ice-water interface and on the seafloor of exo-ocean. Space agencies, including NASA and DLR, are enthusiastic about deploying Exo-AUVs to explore life in these regions. However, the where and how to find life, the technologies to be utilized and the goals to be achieved are crucial aspects for future Exo-AUV life detection missions on Icy Worlds. This study delves into a hypothetical mission of life detection on Europa, discussing science goals,detectable objects, potential regions and biogenic analysis for Icy Worlds. It proposes a life detection strategy for Icy Worlds based on Exo-AUVs, presents key contextual elements for Exo-AUV operations, outlines technological requirements for hull,payloads and autonomy, introduces the current state of Exo-AUV research and addresses existing challenges. This study also suggests a roadmap for conceptual development of Exo-AUV and a Concept of Operations for Multiple Exo-AUV System(ConOps for MEAS). This system aims to assist planetary scientists and astrobiologists in exploring Icy Worlds, identifying robust biosignatures and potentially discovering extant organisms, even prebiotic chemical systems.
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
文摘Profs.Yang Jun(杨军)and Hu Yongyun(胡永云)at the Department of Atmospheric and Oceanic Sciences,School of Physics,Peking University,and their collaborators recently published a paper in Nature Geoscience(http://www.nature.com/ngeo/journal/v10/n8/pdf/ngeo2994.pdf).They show
文摘人类是孤独的,遥望夜空,星汉灿烂!然而,茫茫宇宙,只有地球,是一个生机勃勃、各种生命繁衍不息的星球。Jupiter(木星)有一颗卫星,叫Europa(木卫二),其体积与地球相仿。从Galileo spacecraft传回的信息发现:the presence of water in liquid form on Europa。虽然。科学家们尚不明白whether the water was frozen or in liquid form,但是,他们已经展开了想象的双翅: Even though it is buried beneath a thick layer of ice, life forms could draw energy from heat sources below, just asdeep-sea creatures do in the Earth's oceans. 除了驰骋想象之外,美国国家航空和航天局在“囊中羞涩”之时,仍然决定:to send another spacecraft there!】
文摘SUMMARIES OF TOP NEWS STORIES 42nd Antarctic Expedition Kicked Off China’s 42nd Antarctic expedition team set sail from Shanghai on 1 November.During this expedition,a suite of new technologies will be deployed and tested in the icy wilderness of the Antarctic.
基金supported by Guangdong Basic and Applied Basic Research Foundation(2024A1515012993)the Project of Hunan Provincial Health Commission(No.D202303078877).
文摘Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes.
文摘目的:本研究目的旨在探讨抗PD-1/PD-L1 (程序性细胞死亡蛋白-1,Programmed cell death-1/程序性死亡配体-1,Programmed death-ligand 1)治疗后发生心血管毒性死亡的风险因素,并以此构建预测模型。方法:本研究为单中心回顾性研究,通过系统性回顾方法筛选2018年10月至2023年10月在青岛大学附属医院接受抗PD-1/PD-L1免疫治疗后的2665例实体肿瘤患者的病例资料观察180天,其中发生心血管毒性的33例,根据是否发生抗PD-1/PD-L1治疗心血管毒性死亡为结局,以是否发生死亡分为死亡组和存活组。采用单因素Cox回归分析其风险因素并控制相关混杂因素后构建预测模型绘制列线图。最后,利用受试者工作特征曲线(Receiver Operating Characteristic, ROC)、决策曲线分析法(Decision Curve Analysis, DCA)、校准曲线(Calibration Curve, CC)进行内部评价和内部验证。结果:1) 淋巴细胞计数、单核细胞计数、血小板计数、合并糖尿病、免疫检查点抑制剂种类、彩超室壁运动异常在心血管毒性存活组和死亡组间的差异均有统计学意义(均p Purpose: This study aimed to investigate risk factors for death from cardiovascular toxicity following anti-PD-1/PD-L1 therapy and develop a predictive model. Methods: This study was a single-center retrospective study, which screened the case data of 2665 patients with solid tumors after receiving anti-PD-1/PD-L1 immunotherapy at the Affiliated Hospital of Qingdao University for 180 days of observation by a systematic retrospective method, 33 cases of cardiovascular toxicity, and the outcome was based on whether or not death from cardiovascular toxicity of anti-PD-1/PD-L1 therapy occurred as the outcome categorized into death and survival groups. A one-way Cox regression analysis was used to analyze the risk factors and control for relevant confounders, and a predictive model was constructed to draw a column-line graph. Finally, Receiver Operating Characteristic (ROC), Decision Curve Analysis (DCA), and Calibration Curve (CC) were used for internal evaluation and internal validation. Results: 1) Lymphocyte, Platelet, Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte differences between two groups: those with death from cardiovascular toxicity and those without were statistically significant (all p < 0.05). 2) Univariate Cox regression identified diabetes (HR = 6.03, 95% CI 1.67~21.77, p = 0.006), Types of immune checkpoint inhibitors (HR = 6.62, 95% CI 1.69~25.89, p = 0.007), Echocardiographic ventricular wall motion abnormalities (HR = 4.61, 95% CI 1.19~17.85, p = 0.027), monocyte HR = 0.02, 95% CI 0.00~0.49, p = 0.015) as significant predictors. 3) Multivariate analysis confirmed monocyte (HR = 0.02, 95% CI 0.00~0.77, p = 0.036) as an independent predictor. 4) A predictive model for the risk of death from cardiovascular toxicity was constructed by including 4 variables (p < 0.05) from univariate Cox regression in a nomogram, with an AUC of 0.88 and 95% CI of 0.75 to 1.00. Conclusion: 1) Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte were significant predictors of death from cardiovascular toxicity. 2) Monocyte was an independent protective factor, after adjusting for other covariates. 3) A predictive model for the risk of cardiovascular toxic death was constructed by incorporating 4 variables from univariate Cox regression into a nomogram, and this model had good precision, discrimination, accuracy, and clinical benefit effects.
