The Tibetan Plateau(TP)is the headwater of the Yangtze,Yellow,and the transboundary Yarlung Zangbo,Lancang,and Nujiang Rivers,providing essential and pristine freshwater to around 1.6 billion people in Southeast and S...The Tibetan Plateau(TP)is the headwater of the Yangtze,Yellow,and the transboundary Yarlung Zangbo,Lancang,and Nujiang Rivers,providing essential and pristine freshwater to around 1.6 billion people in Southeast and South Asia.However,the temperature rise TP has experienced is almost three times that of the global warming rate.The rising temperature has resulted in glacier retreat,snow cover reduction,permafrost layer thawing,and so forth.Here we show,based on the longest observed streamflow data available for the region so far,that changing climatic conditions in the TP already had significant impacts on the streamflow in the headwater basins in the area.Our analysis indicated that the annual average temperature in the headwater basins of these five major rivers has been rising on a trend averaging 0.38℃-decade^(-1) since 1998,almost triple the rate before 1998,and the change of streamflow has been predominantly impacted by precipitation in these headwater basins.As a result,streamflow in the Yangtze,Yarlung Zangbo,Lancang,and Nujiang River headwater areas is on a decreasing trend with a reduction of flow ranging from 3.0-10^(9)-5.9-10^(9) m^(3)·decade^(-1)(-9.12%to-16.89%per decade)since 1998.The increased precipitation in the Tangnahai(TNH)and Lanzhou(LZ)Basins contributed to the increase of their streamflows at 8.04%and 14.29%per decade,respectively.Although the increased streamflow in the headwater basins of the Yellow River may ease some of the water resources concerns,the decreasing trend of streamflow in the headwater areas of the southeastern TP region since 1998 could lead to a water crisis in transboundary river basins for billions of people in Southeast and South Asia.展开更多
Traditional microtubule inhibitors fail to significantly enhance+e effect of colorectal cancer;hence,new and efficient strategies are necessary.In+is study,a supramolecular nanoreactor(DOC@TA-Fe^(3+))based on tannic a...Traditional microtubule inhibitors fail to significantly enhance+e effect of colorectal cancer;hence,new and efficient strategies are necessary.In+is study,a supramolecular nanoreactor(DOC@TA-Fe^(3+))based on tannic acid(TA),iron ion(Fe^(3+)),and docetaxel(DOC)wi+microtubule inhibition,reactive oxygen species(ROS)generation,and gluta+ione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,+e DOC@TA-Fe^(3+)nanoreactor escapes from+e lysosomes to release payloads.+e subsequent Fe^(3+)/Fe^(2+)conversion mediated by TA reducibility can trigger+e Fenton reaction to enhance+e ROS concentration.Additionally,Fe^(3+)can consume gluta+ione to repress+e activity of GPX4 to induce ferroptosis.Meanwhile,+e released DOC controls microtubule dynamics to activate+e apoptosis pa+way.+e superior in vivo antitumor efficacy of DOC@TA-Fe^(3+)nanoreactor in terms of tumor grow+inhibition and improved survival is verified in CT26 tumor-bearing mouse model.+erefore,+e nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer+erapy.展开更多
Model parameters estimation is a pivotal issue for runoff modeling in ungauged catchments.The nonlinear relationship between model parameters and catchment descriptors is a major obstacle for parameter regionalization...Model parameters estimation is a pivotal issue for runoff modeling in ungauged catchments.The nonlinear relationship between model parameters and catchment descriptors is a major obstacle for parameter regionalization,which is the most widely used approach.Runoff modeling was studied in 38 catchments located in the Yellow–Huai–Hai River Basin(YHHRB).The values of the Nash–Sutcliffe efficiency coefficient(NSE),coefficient of determination(R2),and percent bias(PBIAS)indicated the acceptable performance of the soil and water assessment tool(SWAT)model in the YHHRB.Nine descriptors belonging to the categories of climate,soil,vegetation,and topography were used to express the catchment characteristics related to the hydrological processes.The quantitative relationships between the parameters of the SWAT model and the catchment descriptors were analyzed by six regression-based models,including linear regression(LR)equations,support vector regression(SVR),random forest(RF),k-nearest neighbor(kNN),decision tree(DT),and radial basis function(RBF).Each of the 38 catchments was assumed to be an ungauged catchment in turn.Then,the parameters in each target catchment were estimated by the constructed regression models based on the remaining 37 donor catchments.Furthermore,the similaritybased regionalization scheme was used for comparison with the regression-based approach.The results indicated that the runoff with the highest accuracy was modeled by the SVR-based scheme in ungauged catchments.Compared with the traditional LR-based approach,the accuracy of the runoff modeling in ungauged catchments was improved by the machine learning algorithms because of the outstanding capability to deal with nonlinear relationships.The performances of different approaches were similar in humid regions,while the advantages of the machine learning techniques were more evident in arid regions.When the study area contained nested catchments,the best result was calculated with the similarity-based parameter regionalization scheme because of the high catchment density and short spatial distance.The new findings could improve flood forecasting and water resources planning in regions that lack observed data.展开更多
A mathematical mechanism of the n-pentane pyrolysis process based on free radical reaction model was presented.The kinetic parameters of n-pentane pyrolysis are obtained by quantum chemistry and the reaction network i...A mathematical mechanism of the n-pentane pyrolysis process based on free radical reaction model was presented.The kinetic parameters of n-pentane pyrolysis are obtained by quantum chemistry and the reaction network is established. The solution of the stiff ordinary differential equations in the n-pentane pyrolysis model is completed by semi implicit Eular algorithm. Then the pyrolysis mechanism based on free radical reaction model is built,and the computational efficiency increases 10 times by algorithm optimization. The validity of this model and its solution method is confirmed by the experimental results of n-pentane pyrolysis.展开更多
First-principles calculations are performed to investigate the effect of strain on the electrochemical performance of Janus MoSSe monolayer.The calculation focuses on the specific capacity,intercalation potential,elec...First-principles calculations are performed to investigate the effect of strain on the electrochemical performance of Janus MoSSe monolayer.The calculation focuses on the specific capacity,intercalation potential,electronic structure,and migration behavior of Li-ion under various strains by using the climbing-image nudged elastic band method.The result shows that the specific capacity is nearly unchanged under strain.But interestingly,the tensile strain can cause the intercalation potential and Li-ion migration energy barrier increase in MoSSe monolayer,whereas the compressive strain can lead to the intercalation potential and energy barrier decreasing.Thus,the rate performance of the MoSSe anode is improved.By analyzing the potential energy surface of MoSSe surface and equilibrium adsorption distance of Li-ion,we explain the physical origin of the change in the intercalation potential and migration energy barrier.The increase of MoSSe potential energy surface and the decrease of adsorption distance caused by tensile strain are the main reason that hinders Li-ion migration.展开更多
LiAIH4 doped with Ni and Ce（SO4）2 additives and the effect of doping on temperature and hydrogen release were studied by pressure-content-temperature （PCT） experiment and X-ray diffraction （XRD） analysis. It is ...LiAIH4 doped with Ni and Ce（SO4）2 additives and the effect of doping on temperature and hydrogen release were studied by pressure-content-temperature （PCT） experiment and X-ray diffraction （XRD） analysis. It is indicated that doping with Ni induces a significant decrease in temperature in the first step and LiA1H4 doped with 1mol% Ni presents the most absorption of hydrogen. Doping with Ce（S04）2 also causes a marked decrease, while the amount of hydrogen release changes only slightly. The results from X-ray diffraction analysis show that doping does not cause any structural change; Ni and Ce-containing phases are not observed at room temoerature or even at 250℃.展开更多
Objective:To explore the clinical method and effect of 3D printing in the treatment of cerebral aneurysms.Methods:The authors research work on the hospital,work time in February 2019-February 2020,this study selected ...Objective:To explore the clinical method and effect of 3D printing in the treatment of cerebral aneurysms.Methods:The authors research work on the hospital,work time in February 2019-February 2020,this study selected patients of cerebral aneurysms,this period are selected for treatment of 100 cases of patients,randomly divided into two groups,a group to give simple intervention,named as the control group,another group for the interventional therapy under the guidance of 3 D printing,named as experimental group,analyze the effect of two groups of patients with clinical intervention.Results:The length of hospital stay in the experimental group was shorter than that in the control group.Meanwhile,the incidence of complications and adverse reactions in the experimental group and the control group were 6.00%and 18.00%,the experimental group was better(P<0.05).Conclusion:3D printing technology can be applied in the treatment of patients with cerebral aneurysms to provide guidance for interventional surgical treatment.It has significant effect,can reduce the incidence complications in patients,has significant clinical effect,and can be popularized.展开更多
Objective:To investigate the clinical effects of applying the magnetic resonance double mismatch technique to endovascular treatment of acute anterior circulation,large vessel occlusion with cerebral infarction in an ...Objective:To investigate the clinical effects of applying the magnetic resonance double mismatch technique to endovascular treatment of acute anterior circulation,large vessel occlusion with cerebral infarction in an unknown time window.Methods:The research work was carried out in our hospital,the work was carried out from November 2018 to November 2019,the patients with acute anterior circulation large vessel occlusion with cerebral infarction who were treated in our hospital during this period,100 patients,50 patients with an unknown time window and 50 patients with definite time window were selected,and they were named as the experimental and control groups,given different examination methods,were given to investigate the clinical treatment effect.Results:Patients’data on HIHSS score before treatment,the incidence of intracranial hemorrhage and rate of Mrs≤2 rating after 90 days of treatment were not significantly different(P>0.05),which was not meaningful.The differences in data between the two groups concerning HIHSS scores were relatively significant before,and after treatment(P<0.05).Conclusion:The magnetic resonance double mismatch technique will be applied in the endovascular treatment of acute anterior circulation large vessel occlusion with cerebral infarction of unknown time window.展开更多
The rapid expansion of renewable energies asks for great progress of energy-storage technologies for sustainable energy supplies,which raises the compelling demand of high-performance rechargeable batteries.To satisfy...The rapid expansion of renewable energies asks for great progress of energy-storage technologies for sustainable energy supplies,which raises the compelling demand of high-performance rechargeable batteries.To satisfy the huge demand from the coming energy-storage market,the resource and cost-effectiveness of rechargeable batteries become more and more important.Manganese(Mn)as a key transition element with advantages including high abundance,low cost,and low toxicity derives various kinds(spinels,layered oxides,polyanions,Prussian blue analogs,etc.)of high-performance Mn-based electrode materials,especially cathodes,for rechargeable batteries ranging from Li-ion batteries,Na-ion batteries,aqueous batteries,to multivalent metal-ion batteries.It is anticipated that Mn-based materials with Mn as the major transition-metal element will constitute a flourishing family of Mn-based rechargeable batteries(Mn RBs)for large-scale and differentiated energy-storage applications.On the other hand,several critical issues including Jahn-Teller effect,Mn dissolution,and O release greatly hinder the pace of Mn RBs,which require extensive material optimizations and battery/system improvements.This review aims to provide an investigation about Mn-based materials and batteries for the coming energy-storage demands,with compelling issues and challenges that must be overcome.展开更多
Nonalcoholic fatty liver disease(NAFLD)is a serious threat to public health,but its underlying mechanism remains poorly understood.In screening important genes using Gene Importance Calculator(GIC)we developed previou...Nonalcoholic fatty liver disease(NAFLD)is a serious threat to public health,but its underlying mechanism remains poorly understood.In screening important genes using Gene Importance Calculator(GIC)we developed previously,ribosomal modification protein rimK-like family member A(RIMKLA)was predicted as one essential gene but its functions remained largely unknown.The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism.RIMKLA expression was reduced in livers of human and mouse with NAFLD.Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice.Hepatocyte-specific RIMKLA knockout aggravated high-fat diet(HFD)-induced dysregulated glucose/lipid metabolism in mice.Mechanistically,RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1(BHMT1)at threonine 45(Thr45)site.Upon phosphorylation at Thr45 and activation,BHMT1 eliminated homocysteine(Hcy)to inhibit the activity of transcription factor activator protein 1(AP1)and its induction on fatty acid synthase(FASn)and cluster of differentiation 36(CD36)gene transcriptions,concurrently repressing lipid synthesis and uptake in hepatocytes.Thr45 to alanine(T45A)mutation inactivated BHMT1 to abolish RIMKLA’s repression on Hcy level,AP1 activity,FASn/CD36 expressions,and lipid deposition.BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes.In summary,RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake.Under obese condition,inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.展开更多
Polydimethylsiloxane containing methacryloyloxy and methoxy silane groups(MAPDMS)-microcapsule-SiO_(2)(MPMS)functional materials were prepared by constructing micro-nano hierarchical structures on the surface of MAPDM...Polydimethylsiloxane containing methacryloyloxy and methoxy silane groups(MAPDMS)-microcapsule-SiO_(2)(MPMS)functional materials were prepared by constructing micro-nano hierarchical structures on the surface of MAPDMS matrix.Herein,MAPDMS@1,1-stilbene-modified hydrolyzed polyglycidyl methacrylate/graphene oxide/dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride(MAPDMS@PGMA_(m)/GO/QC18)self-healing microcapsules with compact multi-shell structure were synthesized and combined with nano-SiO_(2)to construct the hierarchical structures.Furthermore,ultraviolet(UV)/moisture dual curing mode was introduced into deep curing reaction and efficient self-healing reaction of the MPMS.The results show that the introduction of UV/moisture dual curing mode and micro-nano hierarchical structure gives MPMS functional materials excellent mechanical properties,antifouling properties,self-healing properties,antibacterial properties.The shear strength and tensile strength of MPMS increase from 3.32 and 4.26 MPa of MAPDMS to 3.81 and 5.06 MPa,respectively.Its static contact angle increases from 115.9°of MAPDMS to 156.5°,its slide angle decreases from 68.5°of MAPDMS to 7.8°,respectively.The antifouling performance of MPMS against seawater,soy sauce,juice,coffee,protein,other contaminants is effectively improved compared with MAPDMS matrix.At the same time,the tensile strength and elongation at break of MPMS after healing reach 98.22%and 96.57%of those in original state,respectively.In addition,the antibacterial rates of MPMS against Escherichia coli and Staphylococcus aureus reach 99.85%and 100%,respectively.The MPMS prepared in this paper is expected to be widely used in marine antifouling,pipeline network,anti-icing,microfluidics,wearable devices,medical devices,electrochemical biosensors,other fields.展开更多
Single Pilot Operations(SPO),as a NextGen concept of operation,can save both crew costs and human resources for airlines,and has attracted the attention of aviation researchers.To explore in advance the problems that ...Single Pilot Operations(SPO),as a NextGen concept of operation,can save both crew costs and human resources for airlines,and has attracted the attention of aviation researchers.To explore in advance the problems that the introduction of SPO into the aviation system would bring,the Human-Centered Design(HCD)approach has been widely used in the development of SPO.A systematic review of the progress of HCD approach in SPO research can promote further development of SPO.In this paper,the literature resources of SPO were firstly retrieved from scientific research databases by subject search and were used as the input of scientometric analysis to obtain the highly cited literature,the number of annual publications,and the co-authorship network,which enables readers to understand the research trends and research groups of current SPO.Secondly,the development,application,and research process of the HCD approach were introduced in detail,and the progress of the HCD approach in SPO research was reviewed systematically from three aspects:concept design,function allocation,and system evaluation.Finally,limitations of current SPO research and future research directions for applying the HCD approach to SPO were also discussed.展开更多
Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing stud...Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.展开更多
Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclea...Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.展开更多
Commercial aircraft crews have experienced a trend from five-person crew to dual-pilot crew.Arised from both technological and market demands,Single Pilot Operations(SPO)is considered an important development directio...Commercial aircraft crews have experienced a trend from five-person crew to dual-pilot crew.Arised from both technological and market demands,Single Pilot Operations(SPO)is considered an important development direction in modern aviation technology.In this paper,starting from Dual-Pilot Operations(DPO),the piloting process,decision-making process and decisionmaking mode of DPO for commercial aircraft are studied to obtain the operational requirements of SPO.Then,based on above analysis,the operational mechanism of SPO is studied and the core technology of SPO mode is proposed.Next,a new closed frequent bicluster mining algorithm named FsCluster is proposed for the optimization of the SPO model,and the other efficient bicluster mining algorithm named TsCluster is proposed for the analysis and verification of the SPO model.Finally,a typical flight phase scenario is modelled by Magic System of System,and combined with the proposed algorithms for analysis and verification to determine whether the SPO mode can meet the DPO requirements.展开更多
In the present study,2219-T87 Al alloy plates,4 mm in thickness,were subjected to bobbin tool friction stir welding(BTFSW)under relatively high welding speeds of 200 and 400 mm/min,with the aim to analyze the effect o...In the present study,2219-T87 Al alloy plates,4 mm in thickness,were subjected to bobbin tool friction stir welding(BTFSW)under relatively high welding speeds of 200 and 400 mm/min,with the aim to analyze the effect of welding speeds on fatigue properties of the joints.The results showed that the tension–tension high-cycle fatigue performance of the BT-FSW joints at room temperature was significantly enhanced compared to that of other joints of 2xxx series Al alloys counterparts.Particularly at a high welding speed of 400 mm/min,the fatigue strength of the joint reached 78%of the base material together with a high tensile strength of 311 MPa.It was found that the joint line remnants had no effects on the fatigue properties of the BT-FSW joints due to the elimination of root flaws under the action of the lower shoulder.Most of the samples with the welding speed of 200 mm/min failed at the thermo-mechanical zone(TMAZ)during fatigue tests,attributable to the coarsened grains and precipitates,but all of the samples with high welding speed of 400 mm/min randomly failed at the nugget zone due to the improved hardness value in the TMAZ.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the COVID-19 pandemic,has posed severe threats to global public health,highlighting an urgent need to understand its patho...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the COVID-19 pandemic,has posed severe threats to global public health,highlighting an urgent need to understand its pathogenesis and to develop antiviral therapies.Both DNA and RNA viruses can modulate cell cycle progression to maximize their replication.1 However,the effects of SARS-CoV-2 on cell cycle progression remains largely unknown.展开更多
基金funded by the Second Tibetan Plateau Scientific Expedition and Research Program (2019QZKK0203)the National Key Research and Development Programs of China (2021YFC3201100).
文摘The Tibetan Plateau(TP)is the headwater of the Yangtze,Yellow,and the transboundary Yarlung Zangbo,Lancang,and Nujiang Rivers,providing essential and pristine freshwater to around 1.6 billion people in Southeast and South Asia.However,the temperature rise TP has experienced is almost three times that of the global warming rate.The rising temperature has resulted in glacier retreat,snow cover reduction,permafrost layer thawing,and so forth.Here we show,based on the longest observed streamflow data available for the region so far,that changing climatic conditions in the TP already had significant impacts on the streamflow in the headwater basins in the area.Our analysis indicated that the annual average temperature in the headwater basins of these five major rivers has been rising on a trend averaging 0.38℃-decade^(-1) since 1998,almost triple the rate before 1998,and the change of streamflow has been predominantly impacted by precipitation in these headwater basins.As a result,streamflow in the Yangtze,Yarlung Zangbo,Lancang,and Nujiang River headwater areas is on a decreasing trend with a reduction of flow ranging from 3.0-10^(9)-5.9-10^(9) m^(3)·decade^(-1)(-9.12%to-16.89%per decade)since 1998.The increased precipitation in the Tangnahai(TNH)and Lanzhou(LZ)Basins contributed to the increase of their streamflows at 8.04%and 14.29%per decade,respectively.Although the increased streamflow in the headwater basins of the Yellow River may ease some of the water resources concerns,the decreasing trend of streamflow in the headwater areas of the southeastern TP region since 1998 could lead to a water crisis in transboundary river basins for billions of people in Southeast and South Asia.
基金supported by the National Natural Science Foundation of China(Grant Nos.:31971308,81960769,and U1903211)National S&T Major Project(Grant No.:2019ZX09301-147),Luzhou Science and Technology Plan(Grant No.:2018CDLZ10)Sichuan Science and Technology Program(Grant No.:2021YFS0081).
文摘Traditional microtubule inhibitors fail to significantly enhance+e effect of colorectal cancer;hence,new and efficient strategies are necessary.In+is study,a supramolecular nanoreactor(DOC@TA-Fe^(3+))based on tannic acid(TA),iron ion(Fe^(3+)),and docetaxel(DOC)wi+microtubule inhibition,reactive oxygen species(ROS)generation,and gluta+ione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,+e DOC@TA-Fe^(3+)nanoreactor escapes from+e lysosomes to release payloads.+e subsequent Fe^(3+)/Fe^(2+)conversion mediated by TA reducibility can trigger+e Fenton reaction to enhance+e ROS concentration.Additionally,Fe^(3+)can consume gluta+ione to repress+e activity of GPX4 to induce ferroptosis.Meanwhile,+e released DOC controls microtubule dynamics to activate+e apoptosis pa+way.+e superior in vivo antitumor efficacy of DOC@TA-Fe^(3+)nanoreactor in terms of tumor grow+inhibition and improved survival is verified in CT26 tumor-bearing mouse model.+erefore,+e nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer+erapy.
基金financially supported by the National Natural Science Foundation of China(52079026)the National Key Research and Development Program of China(2021YFC3201100)+4 种基金the National Natural Science Foundation of China(41830863 and 61976044)Sichuan Science and Technology Program(2020YFH0037)the Belt and Road Fund on Water and Sustainability of the State Key Laboratory of Hydrology–Water Resources and Hydraulic Engineering(2019nkzd02)the Open Research Fund of State Key Laboratory of Simulation and Regulation of Water Cycle in River Basin(IWHR-SKL-201911)the Fundamental Research Funds for the Central Universities(ZYGX2019Z014)。
文摘径流预报对防洪具有重要意义。然而,由于径流过程的复杂性和随机性,对日径流量进行准确预测是困难的,尤其是对峰值径流量的预测。为了解决这一问题,本研究提出了一种用于径流预测的增强型长短期记忆(LSTM)模型,其中引入了新的损失函数并集成了特征提取器。设计了峰值误差tanh(peak error tanh,PET)和峰值误差swish(peak error swish,PES)两个损失函数,增强了峰值径流预测的重要性,弱化了正常径流预测的权重。为每个气象站建立由3个LSTM网络组成的特征提取器,目的是提取每个气象站输入数据的时间特征。以中国淮河上游为例,利用增强型LSTM模型对1960—2016年的日径流量进行了预测。结果表明,改进后的LSTM模型表现良好,在验证期内(2005年11月至2016年12月),Nash-Sutcliffe效率(NSE)系数在0.917-0.924之间,优于广泛使用的集总水文模型(Australian Water Balance model(AWBM)、Sacramento、Sim Hyd和Tank模型)和数据驱动模型(人工神经网络(ANN)、支持向量回归(SVR)和门控循环单元(GRU))。以PES为损失函数的增强型LSTM对洪水极端径流的预测效果最好,平均NSE为0.873。此外,海拔较高的气象站降水对径流预测的贡献比最近的气象站更大。该研究为流域日径流预测提供了有效工具,有利于流域防洪和水安全管理。
基金funded by the National Key Research and Development Program of China(2017YFA0605002,2017YFA0605004,and 2016YFA0601501)the National Natural Science Foundation of China(41961124007,51779145,and 41830863)“Six top talents”in Jiangsu Province(RJFW-031)。
文摘Model parameters estimation is a pivotal issue for runoff modeling in ungauged catchments.The nonlinear relationship between model parameters and catchment descriptors is a major obstacle for parameter regionalization,which is the most widely used approach.Runoff modeling was studied in 38 catchments located in the Yellow–Huai–Hai River Basin(YHHRB).The values of the Nash–Sutcliffe efficiency coefficient(NSE),coefficient of determination(R2),and percent bias(PBIAS)indicated the acceptable performance of the soil and water assessment tool(SWAT)model in the YHHRB.Nine descriptors belonging to the categories of climate,soil,vegetation,and topography were used to express the catchment characteristics related to the hydrological processes.The quantitative relationships between the parameters of the SWAT model and the catchment descriptors were analyzed by six regression-based models,including linear regression(LR)equations,support vector regression(SVR),random forest(RF),k-nearest neighbor(kNN),decision tree(DT),and radial basis function(RBF).Each of the 38 catchments was assumed to be an ungauged catchment in turn.Then,the parameters in each target catchment were estimated by the constructed regression models based on the remaining 37 donor catchments.Furthermore,the similaritybased regionalization scheme was used for comparison with the regression-based approach.The results indicated that the runoff with the highest accuracy was modeled by the SVR-based scheme in ungauged catchments.Compared with the traditional LR-based approach,the accuracy of the runoff modeling in ungauged catchments was improved by the machine learning algorithms because of the outstanding capability to deal with nonlinear relationships.The performances of different approaches were similar in humid regions,while the advantages of the machine learning techniques were more evident in arid regions.When the study area contained nested catchments,the best result was calculated with the similarity-based parameter regionalization scheme because of the high catchment density and short spatial distance.The new findings could improve flood forecasting and water resources planning in regions that lack observed data.
基金the funding provided by the National Key Research and Development Program of China(2021YFC3200201)the National Natural Science Foundation of China(52121006,U2240203,and 51779144)+2 种基金the Second Tibetan Plateau Scientific Expedition and Research(2019QZKK0203)the Fundamental Research Funds for the Central Universities of China(B210204015 and B210204014)the Consulting Research Project of Chinese Academy of Engineering(2020-ZD-20 and 2021-ZD-CQ-2)。
文摘A mathematical mechanism of the n-pentane pyrolysis process based on free radical reaction model was presented.The kinetic parameters of n-pentane pyrolysis are obtained by quantum chemistry and the reaction network is established. The solution of the stiff ordinary differential equations in the n-pentane pyrolysis model is completed by semi implicit Eular algorithm. Then the pyrolysis mechanism based on free radical reaction model is built,and the computational efficiency increases 10 times by algorithm optimization. The validity of this model and its solution method is confirmed by the experimental results of n-pentane pyrolysis.
基金Project supported by the Education Department of Jiangxi Province,China(Grant No.GJJ160337)。
文摘First-principles calculations are performed to investigate the effect of strain on the electrochemical performance of Janus MoSSe monolayer.The calculation focuses on the specific capacity,intercalation potential,electronic structure,and migration behavior of Li-ion under various strains by using the climbing-image nudged elastic band method.The result shows that the specific capacity is nearly unchanged under strain.But interestingly,the tensile strain can cause the intercalation potential and Li-ion migration energy barrier increase in MoSSe monolayer,whereas the compressive strain can lead to the intercalation potential and energy barrier decreasing.Thus,the rate performance of the MoSSe anode is improved.By analyzing the potential energy surface of MoSSe surface and equilibrium adsorption distance of Li-ion,we explain the physical origin of the change in the intercalation potential and migration energy barrier.The increase of MoSSe potential energy surface and the decrease of adsorption distance caused by tensile strain are the main reason that hinders Li-ion migration.
基金supported by the National High-Tech Research and Development Program (No.2006AA05Z132)the Program of the Ministry of Education of China for Changjiang Scholars and Innovative Research Teams in Universities (No.I2P407)
文摘LiAIH4 doped with Ni and Ce（SO4）2 additives and the effect of doping on temperature and hydrogen release were studied by pressure-content-temperature （PCT） experiment and X-ray diffraction （XRD） analysis. It is indicated that doping with Ni induces a significant decrease in temperature in the first step and LiA1H4 doped with 1mol% Ni presents the most absorption of hydrogen. Doping with Ce（S04）2 also causes a marked decrease, while the amount of hydrogen release changes only slightly. The results from X-ray diffraction analysis show that doping does not cause any structural change; Ni and Ce-containing phases are not observed at room temoerature or even at 250℃.
文摘Objective:To explore the clinical method and effect of 3D printing in the treatment of cerebral aneurysms.Methods:The authors research work on the hospital,work time in February 2019-February 2020,this study selected patients of cerebral aneurysms,this period are selected for treatment of 100 cases of patients,randomly divided into two groups,a group to give simple intervention,named as the control group,another group for the interventional therapy under the guidance of 3 D printing,named as experimental group,analyze the effect of two groups of patients with clinical intervention.Results:The length of hospital stay in the experimental group was shorter than that in the control group.Meanwhile,the incidence of complications and adverse reactions in the experimental group and the control group were 6.00%and 18.00%,the experimental group was better(P<0.05).Conclusion:3D printing technology can be applied in the treatment of patients with cerebral aneurysms to provide guidance for interventional surgical treatment.It has significant effect,can reduce the incidence complications in patients,has significant clinical effect,and can be popularized.
文摘Objective:To investigate the clinical effects of applying the magnetic resonance double mismatch technique to endovascular treatment of acute anterior circulation,large vessel occlusion with cerebral infarction in an unknown time window.Methods:The research work was carried out in our hospital,the work was carried out from November 2018 to November 2019,the patients with acute anterior circulation large vessel occlusion with cerebral infarction who were treated in our hospital during this period,100 patients,50 patients with an unknown time window and 50 patients with definite time window were selected,and they were named as the experimental and control groups,given different examination methods,were given to investigate the clinical treatment effect.Results:Patients’data on HIHSS score before treatment,the incidence of intracranial hemorrhage and rate of Mrs≤2 rating after 90 days of treatment were not significantly different(P>0.05),which was not meaningful.The differences in data between the two groups concerning HIHSS scores were relatively significant before,and after treatment(P<0.05).Conclusion:The magnetic resonance double mismatch technique will be applied in the endovascular treatment of acute anterior circulation large vessel occlusion with cerebral infarction of unknown time window.
基金financially supported by the National Key R&D Program of China(2022YFB2404400)the National Natural Science Foundation of China(92263206,21875007,21975006,21974007,and U19A2018)+1 种基金the Youth Beijing Scholars program(PXM2021_014204_000023)the Beijing Natural Science Foundation(2222001 and KZ202010005007)。
文摘The rapid expansion of renewable energies asks for great progress of energy-storage technologies for sustainable energy supplies,which raises the compelling demand of high-performance rechargeable batteries.To satisfy the huge demand from the coming energy-storage market,the resource and cost-effectiveness of rechargeable batteries become more and more important.Manganese(Mn)as a key transition element with advantages including high abundance,low cost,and low toxicity derives various kinds(spinels,layered oxides,polyanions,Prussian blue analogs,etc.)of high-performance Mn-based electrode materials,especially cathodes,for rechargeable batteries ranging from Li-ion batteries,Na-ion batteries,aqueous batteries,to multivalent metal-ion batteries.It is anticipated that Mn-based materials with Mn as the major transition-metal element will constitute a flourishing family of Mn-based rechargeable batteries(Mn RBs)for large-scale and differentiated energy-storage applications.On the other hand,several critical issues including Jahn-Teller effect,Mn dissolution,and O release greatly hinder the pace of Mn RBs,which require extensive material optimizations and battery/system improvements.This review aims to provide an investigation about Mn-based materials and batteries for the coming energy-storage demands,with compelling issues and challenges that must be overcome.
基金supported by National Natural Science Foundation of China(82300957/82230024/82025008/82070844)Beijing Natural Science Foundation(7212123).
文摘Nonalcoholic fatty liver disease(NAFLD)is a serious threat to public health,but its underlying mechanism remains poorly understood.In screening important genes using Gene Importance Calculator(GIC)we developed previously,ribosomal modification protein rimK-like family member A(RIMKLA)was predicted as one essential gene but its functions remained largely unknown.The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism.RIMKLA expression was reduced in livers of human and mouse with NAFLD.Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice.Hepatocyte-specific RIMKLA knockout aggravated high-fat diet(HFD)-induced dysregulated glucose/lipid metabolism in mice.Mechanistically,RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1(BHMT1)at threonine 45(Thr45)site.Upon phosphorylation at Thr45 and activation,BHMT1 eliminated homocysteine(Hcy)to inhibit the activity of transcription factor activator protein 1(AP1)and its induction on fatty acid synthase(FASn)and cluster of differentiation 36(CD36)gene transcriptions,concurrently repressing lipid synthesis and uptake in hepatocytes.Thr45 to alanine(T45A)mutation inactivated BHMT1 to abolish RIMKLA’s repression on Hcy level,AP1 activity,FASn/CD36 expressions,and lipid deposition.BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes.In summary,RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake.Under obese condition,inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.
基金the financial support from the National Natural Science Foundation of China(No.52003148)the State Key Laboratory of Marine Resource Utilization in South China Sea,Hainan University(No.MRUKF2021023)+3 种基金the Key Research and Development Project of Shaanxi Province(No.2023-YBGY-475)the Key Scientific Research Project of Education Department of Shaanxi Province(No.22JS003)the Industrialization Project of the State Key Laboratory of Biological Resources and Ecological Environment(Cultivation)of Qinba Region(No.SXC-2310)the start-up funds from the Shaanxi University of Technology(No.SLGRCQD2004).
文摘Polydimethylsiloxane containing methacryloyloxy and methoxy silane groups(MAPDMS)-microcapsule-SiO_(2)(MPMS)functional materials were prepared by constructing micro-nano hierarchical structures on the surface of MAPDMS matrix.Herein,MAPDMS@1,1-stilbene-modified hydrolyzed polyglycidyl methacrylate/graphene oxide/dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride(MAPDMS@PGMA_(m)/GO/QC18)self-healing microcapsules with compact multi-shell structure were synthesized and combined with nano-SiO_(2)to construct the hierarchical structures.Furthermore,ultraviolet(UV)/moisture dual curing mode was introduced into deep curing reaction and efficient self-healing reaction of the MPMS.The results show that the introduction of UV/moisture dual curing mode and micro-nano hierarchical structure gives MPMS functional materials excellent mechanical properties,antifouling properties,self-healing properties,antibacterial properties.The shear strength and tensile strength of MPMS increase from 3.32 and 4.26 MPa of MAPDMS to 3.81 and 5.06 MPa,respectively.Its static contact angle increases from 115.9°of MAPDMS to 156.5°,its slide angle decreases from 68.5°of MAPDMS to 7.8°,respectively.The antifouling performance of MPMS against seawater,soy sauce,juice,coffee,protein,other contaminants is effectively improved compared with MAPDMS matrix.At the same time,the tensile strength and elongation at break of MPMS after healing reach 98.22%and 96.57%of those in original state,respectively.In addition,the antibacterial rates of MPMS against Escherichia coli and Staphylococcus aureus reach 99.85%and 100%,respectively.The MPMS prepared in this paper is expected to be widely used in marine antifouling,pipeline network,anti-icing,microfluidics,wearable devices,medical devices,electrochemical biosensors,other fields.
基金This research was funded by the Natural Science Foundation of Shanghai,China(No.20ZR1427800)the New Young Teachers Launch Program of Shanghai Jiao Tong University,China(No.20X100040036).
文摘Single Pilot Operations(SPO),as a NextGen concept of operation,can save both crew costs and human resources for airlines,and has attracted the attention of aviation researchers.To explore in advance the problems that the introduction of SPO into the aviation system would bring,the Human-Centered Design(HCD)approach has been widely used in the development of SPO.A systematic review of the progress of HCD approach in SPO research can promote further development of SPO.In this paper,the literature resources of SPO were firstly retrieved from scientific research databases by subject search and were used as the input of scientometric analysis to obtain the highly cited literature,the number of annual publications,and the co-authorship network,which enables readers to understand the research trends and research groups of current SPO.Secondly,the development,application,and research process of the HCD approach were introduced in detail,and the progress of the HCD approach in SPO research was reviewed systematically from three aspects:concept design,function allocation,and system evaluation.Finally,limitations of current SPO research and future research directions for applying the HCD approach to SPO were also discussed.
基金We thank the families for participation in this study,and we thank Novogene Technology Co.,Ltd.,for the WES sequencing and analysis.This work was supported by the National Natural Science Foundation Project of China(82070951,82271078)the National Natural Science Foundation Key Program(81930023)+3 种基金The Innovative Research Group Project of Chongqing Education Commission(CXQT19015)the Innovation Supporting Plan of Overseas Study of Chongqing(cx2018010)the National Key Clinical Specialties Construction Program of China,the Chongqing Branch of the National Clinical Research Center for Ocular Diseases,the Chongqing Key Laboratory of Ophthalmology(CSTC,2008CA5003)the Program for Youth Innovation in Future Medicine,Chongqing Medical University(w0047).
文摘Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.
基金supported by the National Natural Science Foundation Project of China(No.82070951,82271078 and 81873678)the Innovative Research Group Project of Chongqing Education Commission(China)(No.CXQT19015)+5 种基金the Natural Science Foundation Project of Chongqing,China(No.cstc2019jcyjmsxmx0120)the Innovation Supporting Plan of Overseas Study of Chongqing,China(No.cx2018010)the Chongqing Education Commission(China)(No.KJQN202000406)the National Key Clinical Specialties Construction Program of China,Chongqing Branch of National Clinical Research Center for Ocular Diseasesthe Chongqing Key Laboratory of Ophthalmology(China)(CSTC,No.2008CA5003)Natural Science Foundation Project of Chongqing Medical University(China)(No.W0047).
文摘Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.
基金sponsored by the Natural Science Foundation of Shanghai(No.20ZR1427800)the New Young Teachers Launch Program of Shanghai Jiaotong University,China(No.20X100040036)+1 种基金the National Natural Science Foundation of China(No.61971273)the Development Program in Shaanxi Province of China(No.2021GY-032)。
文摘Commercial aircraft crews have experienced a trend from five-person crew to dual-pilot crew.Arised from both technological and market demands,Single Pilot Operations(SPO)is considered an important development direction in modern aviation technology.In this paper,starting from Dual-Pilot Operations(DPO),the piloting process,decision-making process and decisionmaking mode of DPO for commercial aircraft are studied to obtain the operational requirements of SPO.Then,based on above analysis,the operational mechanism of SPO is studied and the core technology of SPO mode is proposed.Next,a new closed frequent bicluster mining algorithm named FsCluster is proposed for the optimization of the SPO model,and the other efficient bicluster mining algorithm named TsCluster is proposed for the analysis and verification of the SPO model.Finally,a typical flight phase scenario is modelled by Magic System of System,and combined with the proposed algorithms for analysis and verification to determine whether the SPO mode can meet the DPO requirements.
基金financially supported by the LiaoNing Revitalization Talents Program under grant No.XLYC2002099the LiaoNing Province Excellent Youth Foundation(No.2021-YQ-01)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.Y2021061)the IMR Innovation Fund(No.2022-PY11).
文摘In the present study,2219-T87 Al alloy plates,4 mm in thickness,were subjected to bobbin tool friction stir welding(BTFSW)under relatively high welding speeds of 200 and 400 mm/min,with the aim to analyze the effect of welding speeds on fatigue properties of the joints.The results showed that the tension–tension high-cycle fatigue performance of the BT-FSW joints at room temperature was significantly enhanced compared to that of other joints of 2xxx series Al alloys counterparts.Particularly at a high welding speed of 400 mm/min,the fatigue strength of the joint reached 78%of the base material together with a high tensile strength of 311 MPa.It was found that the joint line remnants had no effects on the fatigue properties of the BT-FSW joints due to the elimination of root flaws under the action of the lower shoulder.Most of the samples with the welding speed of 200 mm/min failed at the thermo-mechanical zone(TMAZ)during fatigue tests,attributable to the coarsened grains and precipitates,but all of the samples with high welding speed of 400 mm/min randomly failed at the nugget zone due to the improved hardness value in the TMAZ.
基金This work was supported by grant from the National Natural Science Foundation of China(81972873,82002165,81871699,and 82072330)the Biosafety Research Special Plan of the Logistics Support Department of the Military Commission(923070201202)+5 种基金the young and middle-aged science and technology innovation leaders and teams of the Jilin Provincial Department of Science and Technology(20200301001RQ)China Ministry of Science and Technology Key Research and Development Program(2022YFF1203204)Jilin Province Pathogen and Infection Informatics International Joint Research Center(20210504004GH)the Pearl River Talent Plan in Guangdong Province of China(2019CX01N111)the Scientific and Technological Research Projects of Guangzhou,China(202103000008)the Medical Innovation Team Project of Jilin University(2022JBGS02).
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the COVID-19 pandemic,has posed severe threats to global public health,highlighting an urgent need to understand its pathogenesis and to develop antiviral therapies.Both DNA and RNA viruses can modulate cell cycle progression to maximize their replication.1 However,the effects of SARS-CoV-2 on cell cycle progression remains largely unknown.
