Objective:Migrasomes,an emerging class of migration-facilitating membranous extracellular vesicles,remain largely uncharted in the intricate landscape of tumor metastasis.This study aimed to illuminate the roles and m...Objective:Migrasomes,an emerging class of migration-facilitating membranous extracellular vesicles,remain largely uncharted in the intricate landscape of tumor metastasis.This study aimed to illuminate the roles and mechanisms underlying cancer cell-derived migrasomes in breast cancer brain metastasis(BCBM).Methods:Migrasomes were isolated and purified from BCBM cells(231-BR)and non-specific organotropic parental counterparts(MDA-MB-231),specifically designated as Mig-BCBM and Mig-BC,respectively.The role of Mig-BCBM in BCBM was investigated using an in vitro endothelial cell layer permeability model and a BCBM mouse model.The regulatory mechanism underlying Mig-BCBM was assessed using RT-qPCR,western blotting,immunofluorescence,ex vivo fluorescence imaging,and a series of rescue experiments.Results:Mig-BCBM potently augmented the permeability of vascular endothelial layers,which facilitated the efficient migration of 231-BR cells across endothelial barriers in vitro.The administration of Mig-BCBM significantly disrupted the blood-brain barrier(BBB)and accelerated BCBM progression in vivo,as evidenced in mouse models,compared to the Mig-BC and control groups.Mechanistically,Mig-BCBM harbored ATF6,a critical transducer of endoplasmic reticulum(ER)stress.Upon internalization into hCMEC/D3 cells,ATF6 elicited robust ER stress responses,culminating in downregulation of ZO-1 and VE-cadherin.Digital PCR analysis disclosed significant upregulation of ATF6 in serum migrasomes derived from BCBM patients compared to migrasomes from breast cancer patients and healthy individuals.Conclusions:This study uncovered a pivotal role of cancer cell-derived in BCBM by harnessing ATF6-mediated ER stress to disrupt the BBB and promote metastasis,suggesting novel diagnostic and therapeutic strategies targeting migrasomes and migrasome cargo.展开更多
A new fluorescent method was developed based on the ulifloxacin-europium（Ⅲ）-sodium dodecylbenzene sulfonate system for the determination of ulifloxacin,the active metabolite of prulifloxacin.Sodium dodecylbenzene s...A new fluorescent method was developed based on the ulifloxacin-europium（Ⅲ）-sodium dodecylbenzene sulfonate system for the determination of ulifloxacin,the active metabolite of prulifloxacin.Sodium dodecylbenzene sulfonate formed a ternary complex with ulifloxacin-europium（Ⅲ）and significantly enhanced the characteristic fluorescence of europium（Ⅲ）.The enhanced fluorescence intensity showed a good linear relationship with the concentration of ulifloxacin in the range of 5.0×10^-8-2.0×10^-6M with a detection limit of 2.0×10^-10 M（3σ）.This method is rapid and sensitive,and has been successfully applied to the determination of ulifloxacin in human urine and serum samples.展开更多
Dimension-reduced and decentralized learning i always viewed as an efficient way to solve multi-agent cooperative learning in high dimension. However, the dynamic environmen brought by the concurrent learning makes th...Dimension-reduced and decentralized learning i always viewed as an efficient way to solve multi-agent cooperative learning in high dimension. However, the dynamic environmen brought by the concurrent learning makes the decentralized learning hard to converge and bad in performance. To tackle thi problem, a timesharing-tracking framework(TTF), stemming from the idea that alternative learning in microscopic view results in concurrent learning in macroscopic view, is proposed in this paper, in which the joint-state best-response Q-learning(BRQ-learning) serves as the primary algorithm to adapt to the companions policies. With the properly defined switching principle, TTF makes all agents learn the best responses to others at different joint states. Thus from the view of the whole joint-state space, agents learn the optimal cooperative policy simultaneously. The simulation results illustrate that the proposed algorithm can learn the optimal joint behavior with les computation and faster speed compared with other two classica learning algorithms.展开更多
Background:In recent years,there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data(RCD).These studies rely on algorithms to identify specific hea...Background:In recent years,there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data(RCD).These studies rely on algorithms to identify specific health conditions(e.g.,diabetes or sepsis)for statistical analyses.However,there has been substantial variation in the algorithm development and validation,leading to frequently suboptimal performance and posing a significant threat to the validity of study findings.Unfortunately,these issues are often overlooked.Methods:We systematically developed guidance for the development,validation,and evaluation of algorithms designed to identify health status(DEVELOP-RCD).Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development,validation,and evaluation.Subsequently,we conducted an empirical study on an algorithm for identifying sepsis.Based on these findings,we formulated specific workflow and recommendations for algorithm development,validation,and evaluation within the guidance.Finally,the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it.Results:A standardized workflow for algorithm development,validation,and evaluation was established.Guided by specific health status considerations,the workflow comprises four integrated steps:assessing an existing algorithm’s suitability for the target health status;developing a new algorithm using recommended methods;validating the algorithm using prescribed performance measures;and evaluating the impact of the algorithm on study results.Additionally,13 good practice recommendations were formulated with detailed explanations.Furthermore,a practical study on sepsis identification was included to demonstrate the application of this guidance.Conclusions:The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD.This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.展开更多
As a wide-bandgap semiconductor(WBG), β-Ga_2O_3 is expected to be applied to power electronics and solar blind UV photodetectors. In this review, defects in β-Ga_2O_3 single crystals were summarized, including dislo...As a wide-bandgap semiconductor(WBG), β-Ga_2O_3 is expected to be applied to power electronics and solar blind UV photodetectors. In this review, defects in β-Ga_2O_3 single crystals were summarized, including dislocations, voids, twin, and small defects. Their effects on device performance were discussed. Dislocations and their surrounding regions can act as paths for the leakage current of SBD in single crystals. However, not all voids lead to leakage current. There's no strong evidence yet to show small defects affect the electrical properties. Doping impurity was definitely irrelated to the leakage current. Finally, the formation mechanism of the defects was analyzed. Most small defects were induced by mechanical damages. The screw dislocation originated from a subgrain boundary. The edge dislocation lying on a plane slightly tilted towards the(102) plane, the(101) being the possible slip plane. The voids defects like hollow nanopipes, PNPs, NSGs and line-shaped grooves may be caused by the condensation of excess oxygen vacancies, penetration of tiny bubbles or local meltback. The nucleation of twin lamellae occurred at the initial stage of "shoulder part" during the crystal growth. These results are helpful in controlling the occurrence of crystal defects and improving the device performance.展开更多
The thermal scratch significantly influences the surface quality of the stainless steel in cold strip rolling. The thermal scratch has a close relation to the rolling parameters, the rolls surface and the emulsions us...The thermal scratch significantly influences the surface quality of the stainless steel in cold strip rolling. The thermal scratch has a close relation to the rolling parameters, the rolls surface and the emulsions used in rolling. In order to explain the thermal scratch on the strip surface, the cold roiling process of SUS430 stainless steel strip was investigated in the laboratory. The thermal scratch defect occurs frequently in the second rolling pass （maximum reduction in height is 32.3 ~）, especially on the lower surface of strips. When concentration and temperature of the emulsion are the same, the thermal scratch on the surface o{ the strip is aggravated with increasing the roll surface roughness. With the same roll surface roughness and emulsion concentration, the thermal scratch is obviously more severe at an emulsion temperature of 63 ℃ than 55 ℃. With the same roll surface roughness and emulsion tempera- ture, the thermal scratch is distinctly weaker at the emulsion concentration of 6 % than that of 3 %.展开更多
We consider quadratic stabilization for a class of switched systems which are composed of a finite set of continuoustime linear subsystems with norm bounded uncertainties. Under the assumption that there is no single ...We consider quadratic stabilization for a class of switched systems which are composed of a finite set of continuoustime linear subsystems with norm bounded uncertainties. Under the assumption that there is no single quadratically stable subsystem, if a convex combination of subsystems is quadratically stable, then we propose a state-dependent switching law, based on the convex combination of subsystems, such that the entire switched linear system is quadratically stable. When the state information is not available, we extend the discussion to designing an outputdependent switching law by constructing a robust Luenberger observer for each subsystem.展开更多
Since September 2011,A 2/O-MBR wastewater treatment plant in Xi'an Siyuan University has been successfully running without replacing any of membrane modules.A total of 6.661 million m^3 of campus wastewater has be...Since September 2011,A 2/O-MBR wastewater treatment plant in Xi'an Siyuan University has been successfully running without replacing any of membrane modules.A total of 6.661 million m^3 of campus wastewater has been treated,and 4.405 million m^3 of water reaching the national urban miscellaneous water standard has been reclaimed and reused.A total of 25 km pipeline,5 pits,scenery fountains,lakes,and 12 pump stations have been constructed for flushing toilets,irrigating green grass lawn and afforest,and cleaning hardened pavement.The design and construction of 5 pits,scenery fountains,and lakes are important to meet the national urban miscellaneous water standard under occasional phosphorus and/or nitrogen exceed concentration.The unit water cost is 4.19 yuan/m^3,including membrane modules depreciation and amortization.After the A 2/O-MBR system passes the membrane modules depreciation and amortization period,the unit water cost is 2.82 yuan/m^3.The water productivity of the membrane stack rises first at the beginning of operation,reaches the maximum value,and then decreases.The average annual transmembrane pressure difference increases by 1.12 kPa.The average VMD of industrial permeability decreases annually by 0.45 m^3.展开更多
Individual countries are requested to submit nationally determined contributions(NDCs)to alleviate global warming in the Paris Agreement.However,the global climate effects and regional contributions are not explicitly...Individual countries are requested to submit nationally determined contributions(NDCs)to alleviate global warming in the Paris Agreement.However,the global climate effects and regional contributions are not explicitly considered in the countries’decision-making process.In this study,we evaluate the global temperature slowdown of the NDC scenario(ΔT=0.6°C)and attribute the global temperature slowdown to certain regions of the world with a compact earth system model.Considering reductions in CO_(2),CH_(4),N_(2)O,BC,and SO_(2),the R5OECD(the Organization for Economic Co-operation and Development in 1990)and R5ASIA(Asian countries)are the top two contributors to global warming mitigation,accounting for 39.3%and 36.8%,respectively.R5LAM(Latin America and the Caribbean)and R5MAF(the Middle East and Africa)followed behind,with contributions of 11.5%and 8.9%,respectively.The remaining 3.5%is attributed to R5REF(the Reforming Economies).Carbon Dioxide emission reduction is the decisive factor of regional contributions,but not the only one.Other greenhouse gases are also important,especially for R5MAF.The contribution of short-lived aerosols is small but significant,notably SO_(2)reduction in R5ASIA.We argue that additional species beyond CO_(2)need to be considered,including short-lived pollutants,when planning a route to mitigate climate change.It needs to be emphasized that there is still a gap to achieve the Paris Agreement 2-degree target with current NDC efforts,let alone the ambitious 1.5-degree target.All countries need to pursue stricter reduction policies for a more sustainable world.展开更多
From the roots of Ligularia macrophylla, a bisesquiterpene, ligumacrophyllal was isolated and its structure was elucidated on the basis of spectroscopic methods.
A new bisabolane sesquiterpene, 5 beta-acetoxy-4 beta, 8-diangeloyloxy-2 beta,3 beta, :10,11-diepoxy-bisabola-7 (14)-ene, was isolated from the roots of Ligularia songarica and its structure was elucidated on the basi...A new bisabolane sesquiterpene, 5 beta-acetoxy-4 beta, 8-diangeloyloxy-2 beta,3 beta, :10,11-diepoxy-bisabola-7 (14)-ene, was isolated from the roots of Ligularia songarica and its structure was elucidated on the basis of spectroscopic methods, especially 2D-NMR techniques.展开更多
We study the behaviors of three-dimensional double and triple Weyl fermions in the presence of weak random potential.By performing the Wilsonian renormalization group(RG)analysis,we reveal that the quasiparticle exper...We study the behaviors of three-dimensional double and triple Weyl fermions in the presence of weak random potential.By performing the Wilsonian renormalization group(RG)analysis,we reveal that the quasiparticle experiences strong renormalization which leads to the modification of the density of states and quasiparticle residue.We further utilize the RG analysis to calculate the classical conductivity and show that the diffusive transport is substantially corrected due to the novel behavior of the quasiparticle and can be directly measured by experiments.展开更多
BACKGROUND Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of drugs for treating renal anemia.It is a second-generation hypoxia-inducible factor prolyl hydroxylase-2(PHD2)inhibitor.Roxadustat can ...BACKGROUND Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of drugs for treating renal anemia.It is a second-generation hypoxia-inducible factor prolyl hydroxylase-2(PHD2)inhibitor.Roxadustat can effectively increase hemoglobin in patients with dialysis-dependent chronic kidney disease,with an adverse events profile comparable to that of epoetin alfa.We administered roxadustat to a maintenance hemodialysis patient who was allergic to erythropoiesis-stimulating agents(ESAs)and depended on blood transfusion for five years.After applying Roxadustat,the patient’s anemia improved significantly.CASE SUMMARY A 77-year-old Chinese man had type 2 diabetes for 16 years,underwent maintenance hemodialysis for five years,and had fatigue for five years.Laboratory tests showed severe anemia(hemoglobin concentration of 42 g/L).The patient was administered a subcutaneous injection of ESAs before dialysis.He suffered an allergic shock immediately and fainted.His blood pressure dropped to undetectable levels.He was not administered ESAs henceforth.The patient was prescribed iron supplements and received blood transfusions occasionally for five years.His hemoglobin concentration ranged from 42-68 g/L.After taking six weeks of oral roxadustat three times weekly(100 mg TIW),the patient’s hemoglobin concentration increased significantly,and his symptoms decreased.We adjusted the doses of roxadustat,and the hemoglobin concentration was maintained between 97 and 126 g/L.CONCLUSION Oral roxadustat is effective in treating anemia in maintenance hemodialysis patients who cannot be administered ESAs.展开更多
Dear Editor,This letter is concerned with quadratic L_(2) performance(quadratic stability and L_(2) gain)for switched uncertain linear systems(SULS)with norm-bounded uncertainties.Assuming that no single uncertain sub...Dear Editor,This letter is concerned with quadratic L_(2) performance(quadratic stability and L_(2) gain)for switched uncertain linear systems(SULS)with norm-bounded uncertainties.Assuming that no single uncertain subsystem achieves quadratic L_(2) performanceγbut a convex combination of the subsystems can make it,we propose a state-dependent switching law such that the SULS achieves the desired quadratic L_(2) performance.The discussion is extended to the SULS with state feedback control,and a sufficient condition is proposed to design the state feedback gains and the switching law simultaneously.展开更多
We report an exact numerical study on disorder effect in double-Weyl semimetals,and compare exact numerical solutions for the quasiparticle behavior with the Born approximation and renormalization group results.It is ...We report an exact numerical study on disorder effect in double-Weyl semimetals,and compare exact numerical solutions for the quasiparticle behavior with the Born approximation and renormalization group results.It is revealed that the low-energy quasiparticle properties are renormalized by multiple-impurity scattering processes,leading to apparent power-law behavior of the self-energy.Therefore,the quasiparticle residue surrounding nodal points is considerably reduced and vanishes as ZE∝Er with nonuniversal exponent.We show that such unusual behavior of the quasiparticle leads to strong temperature dependence of diffusive conductivity.Remarkably,we also find a universal minimum conductivity along the direction of linear dispersion at the nodal point,which can be directly observed by experimentalist.展开更多
AIM：To identify the effects of interleukin（IL）-13 on retinal pigment epithelial（RPE） cells and the IL-13 level in aqueous humor of age-related macular degeneration（AMD） patients.METHODS：IL-13 levels in aqueous...AIM：To identify the effects of interleukin（IL）-13 on retinal pigment epithelial（RPE） cells and the IL-13 level in aqueous humor of age-related macular degeneration（AMD） patients.METHODS：IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay（ELISA）.ARPE-19 cells were treated with 10 ng/m L IL-13 for 12,24,and 48 h.The cell proliferaton was evaluated by the MTS method.The m RNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction（q RT-PCR） and Western blot respectively.The expression of tumor necrosis factor-α（TNF-α）,transforming growth factor-β（TGF-β） and vascular endothelial growth factor（VEGF） were assessed by ELISA.RESU LTS：IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control（167.33±17.64 vs 27.12±5.65 pg/m L;P〈0.01）.In vit ro,IL-13 of high concentrations（10,15,and 20 ng/m L） inhibited ARPE-19 cell proliferation.α-SMA m RNA in ARPE-19 cell were increased（1.017±0.112 vs 1.476±0.168;P〈0.001） and ZO-1 decreased（1.051±0.136 vs 0.702±0.069;P〈0.001） after treated with 10 ng/m L IL-13 for 48 h.The protein expression of α-SMA and ZO-1 also showed the same tendency（α-SMA：P=0.038;ZO-1：P=0.008）.IL-13 significantly reduced the level of TNF-α（44.70±1.67 vs 31.79±3.53 pg/m L;P=0.005） at 48 h,but the le vel of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/m L at 24h（P=0.004） and from 61.26±1.11 to 86.91±3.59 pg/m L at 48h（P〈0.001）.While expressions of VEGF didn＇t change after IL-13 treatment.CONCLUSION：IL-13 in vitr o inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.展开更多
BACKGROUND:Experimental autoimmune myasthenia gravis(EAMG)and anti-AchR antibody of human myasthenia gravis are the same immune globulin.This antibody restricts the activity of nicotinic acetylcholine receptor and the...BACKGROUND:Experimental autoimmune myasthenia gravis(EAMG)and anti-AchR antibody of human myasthenia gravis are the same immune globulin.This antibody restricts the activity of nicotinic acetylcholine receptor and the amount of receptor binding sites is decreased,so myasthenia gravis occurs.OBJECTIVE:To observe the therapeutic effect and mechanism of action of Qiangjijianli capsule on EAMG rats.DESIGN:A randomized controlled animal experiment.SETTING:Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine.MATERIALS:Acetylcholine receptors(AchR)were extracted from electric skate's electric organ which lives in the sea near Guangzhou.It had high biological activity and the protein content was 1.63 g/L.Qiangjijianli capsule(Astragalus mongholicus,Codonopsis pilosula,Atractylodes macrocephala,Angelica sinensis,Bupleurum chinense,Cairo morningglory root or leaf,Glycyrrhiza uralensis,etc.0.5 g crude drug per capsule)was bought from the Manufacturing Laboratory of Guangzhou University of Traditional Chinese Medicine with the Batch No.89-11-1.METHODS:This experiment was carried out in the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine from May to August 1990.①Adult female SD rats were immunized with AchR.The animals'movement condition was observed and recorded everyday.Ten rats were chosen as normal control group,and they were not given any treatment and raised normally.After modeled,20 successful rats were randomly assigned into 2 groups:treatmental group and model group.2 mL Qiangjijianli capsule suspension(1 g)was intragastrically administrated into each rat of treatmental group for 30 days;The same amount of clean water was intragastrically administrated into the rats of model group for 30 days.②Serum AchR antibody was measured with ABC-ELISA method.After administration,the rats were sacrificed.The complete diaphragmatic muscle was extracted for in vitro receptor binding test.The constitution of N-AchR per milligram of tissue was measured with FT-603 well-typeγscintillation detector and FH408 calibrater.③t test was used for the comparison of difference of mean value of two samples.MAIN OUTCOME MEASURES:The effect of Qiangjijianli capsule on the amount of binding site of serum AchR antibody and nicotine-like acetylcholinergic receptor(N-AChR).RESULTS:Before Qiangjijianli capsule treatment,serum AchR antibody titre was close between model group and treatmental group(0.82±0.15 vs.0.79±0.12,P>0.05);After Qiangjijianli capsule treatment,serum AchR antibody titre of treatmental group was significantly decreased(0.45±0.11,t=6.602,P<0.01),and that in the treatmental group did not change significantly(0.71±0.13,P>0.05).So,serum AchR antibody titre of treatmental group was significantly lower than that of model group(t=5.780,P<0.01).③The number of N-AchR of normal control group was significantly more than that of model group[(1503±156)mg·min-1 vs.(1118±128)mg·min-1,t=6.034,P<0.01].The number of N-AchR of treatmental group was significantly more than that of model group[(1277±143)mg·min^(-1)vs.(1118±128)mg·min^(-1),t=2.619,P<0.05].③After the treatment of Qiangjijianli capsule,all of the six rats which had clinical symptoms in treatmental group did well more or less,while in model group,the six rats had no change except one.CONCLUSION:Qiangjijianli capsule can improve the symptoms of myasthenia gravis by immunological regulation and pharmacological effect of N-AchR.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81702884)Natural Science Foundation of Shandong Province(Grant Nos.ZR2022MH272,ZR2020QH216,and ZR2023QH115)Medicine and Health Science and Technology Foundation of Shandong Province(Grant Nos.202402060623 and 202202080721).
文摘Objective:Migrasomes,an emerging class of migration-facilitating membranous extracellular vesicles,remain largely uncharted in the intricate landscape of tumor metastasis.This study aimed to illuminate the roles and mechanisms underlying cancer cell-derived migrasomes in breast cancer brain metastasis(BCBM).Methods:Migrasomes were isolated and purified from BCBM cells(231-BR)and non-specific organotropic parental counterparts(MDA-MB-231),specifically designated as Mig-BCBM and Mig-BC,respectively.The role of Mig-BCBM in BCBM was investigated using an in vitro endothelial cell layer permeability model and a BCBM mouse model.The regulatory mechanism underlying Mig-BCBM was assessed using RT-qPCR,western blotting,immunofluorescence,ex vivo fluorescence imaging,and a series of rescue experiments.Results:Mig-BCBM potently augmented the permeability of vascular endothelial layers,which facilitated the efficient migration of 231-BR cells across endothelial barriers in vitro.The administration of Mig-BCBM significantly disrupted the blood-brain barrier(BBB)and accelerated BCBM progression in vivo,as evidenced in mouse models,compared to the Mig-BC and control groups.Mechanistically,Mig-BCBM harbored ATF6,a critical transducer of endoplasmic reticulum(ER)stress.Upon internalization into hCMEC/D3 cells,ATF6 elicited robust ER stress responses,culminating in downregulation of ZO-1 and VE-cadherin.Digital PCR analysis disclosed significant upregulation of ATF6 in serum migrasomes derived from BCBM patients compared to migrasomes from breast cancer patients and healthy individuals.Conclusions:This study uncovered a pivotal role of cancer cell-derived in BCBM by harnessing ATF6-mediated ER stress to disrupt the BBB and promote metastasis,suggesting novel diagnostic and therapeutic strategies targeting migrasomes and migrasome cargo.
基金supported by the National Natural Science Foundation of China(Nos.20875056,20775043)
文摘A new fluorescent method was developed based on the ulifloxacin-europium（Ⅲ）-sodium dodecylbenzene sulfonate system for the determination of ulifloxacin,the active metabolite of prulifloxacin.Sodium dodecylbenzene sulfonate formed a ternary complex with ulifloxacin-europium（Ⅲ）and significantly enhanced the characteristic fluorescence of europium（Ⅲ）.The enhanced fluorescence intensity showed a good linear relationship with the concentration of ulifloxacin in the range of 5.0×10^-8-2.0×10^-6M with a detection limit of 2.0×10^-10 M（3σ）.This method is rapid and sensitive,and has been successfully applied to the determination of ulifloxacin in human urine and serum samples.
文摘Dimension-reduced and decentralized learning i always viewed as an efficient way to solve multi-agent cooperative learning in high dimension. However, the dynamic environmen brought by the concurrent learning makes the decentralized learning hard to converge and bad in performance. To tackle thi problem, a timesharing-tracking framework(TTF), stemming from the idea that alternative learning in microscopic view results in concurrent learning in macroscopic view, is proposed in this paper, in which the joint-state best-response Q-learning(BRQ-learning) serves as the primary algorithm to adapt to the companions policies. With the properly defined switching principle, TTF makes all agents learn the best responses to others at different joint states. Thus from the view of the whole joint-state space, agents learn the optimal cooperative policy simultaneously. The simulation results illustrate that the proposed algorithm can learn the optimal joint behavior with les computation and faster speed compared with other two classica learning algorithms.
基金supported by the National Natural Science Foundation of China(82225049,72104155)the Sichuan Provincial Central Government Guides Local Science and Technology Development Special Project(2022ZYD0127)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD23004).
文摘Background:In recent years,there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data(RCD).These studies rely on algorithms to identify specific health conditions(e.g.,diabetes or sepsis)for statistical analyses.However,there has been substantial variation in the algorithm development and validation,leading to frequently suboptimal performance and posing a significant threat to the validity of study findings.Unfortunately,these issues are often overlooked.Methods:We systematically developed guidance for the development,validation,and evaluation of algorithms designed to identify health status(DEVELOP-RCD).Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development,validation,and evaluation.Subsequently,we conducted an empirical study on an algorithm for identifying sepsis.Based on these findings,we formulated specific workflow and recommendations for algorithm development,validation,and evaluation within the guidance.Finally,the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it.Results:A standardized workflow for algorithm development,validation,and evaluation was established.Guided by specific health status considerations,the workflow comprises four integrated steps:assessing an existing algorithm’s suitability for the target health status;developing a new algorithm using recommended methods;validating the algorithm using prescribed performance measures;and evaluating the impact of the algorithm on study results.Additionally,13 good practice recommendations were formulated with detailed explanations.Furthermore,a practical study on sepsis identification was included to demonstrate the application of this guidance.Conclusions:The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD.This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.
基金the Financial support from the National key Research and Development Program of China(Nso.2018YFB0406502,2016YFB1102201)the National Natural Science Foundation of China(Grant No.51321091)+2 种基金the key Research and Development Program of Shandong Province(No.2018CXGC0410)the Young Scholars Program of Shandong University(No.2015WLJH36)the 111 Project 2.0(No.BP2018013)
文摘As a wide-bandgap semiconductor(WBG), β-Ga_2O_3 is expected to be applied to power electronics and solar blind UV photodetectors. In this review, defects in β-Ga_2O_3 single crystals were summarized, including dislocations, voids, twin, and small defects. Their effects on device performance were discussed. Dislocations and their surrounding regions can act as paths for the leakage current of SBD in single crystals. However, not all voids lead to leakage current. There's no strong evidence yet to show small defects affect the electrical properties. Doping impurity was definitely irrelated to the leakage current. Finally, the formation mechanism of the defects was analyzed. Most small defects were induced by mechanical damages. The screw dislocation originated from a subgrain boundary. The edge dislocation lying on a plane slightly tilted towards the(102) plane, the(101) being the possible slip plane. The voids defects like hollow nanopipes, PNPs, NSGs and line-shaped grooves may be caused by the condensation of excess oxygen vacancies, penetration of tiny bubbles or local meltback. The nucleation of twin lamellae occurred at the initial stage of "shoulder part" during the crystal growth. These results are helpful in controlling the occurrence of crystal defects and improving the device performance.
基金Sponsored by National Natural Science Foundation of China(51174057,51274062)National High-technology Researchand Development Program of China(2012AA03A503)
文摘The thermal scratch significantly influences the surface quality of the stainless steel in cold strip rolling. The thermal scratch has a close relation to the rolling parameters, the rolls surface and the emulsions used in rolling. In order to explain the thermal scratch on the strip surface, the cold roiling process of SUS430 stainless steel strip was investigated in the laboratory. The thermal scratch defect occurs frequently in the second rolling pass （maximum reduction in height is 32.3 ~）, especially on the lower surface of strips. When concentration and temperature of the emulsion are the same, the thermal scratch on the surface o{ the strip is aggravated with increasing the roll surface roughness. With the same roll surface roughness and emulsion concentration, the thermal scratch is obviously more severe at an emulsion temperature of 63 ℃ than 55 ℃. With the same roll surface roughness and emulsion tempera- ture, the thermal scratch is distinctly weaker at the emulsion concentration of 6 % than that of 3 %.
基金supported in part by the Japan Ministry of Education,Sciences and Culture under Grants-in-Aid for Scientific Research(C)(21560471)the Green Industry Leading Program of Hubei University of Technology(CPYF2017003)the National Natural Science Foundation of China(1160147411461082)
文摘We consider quadratic stabilization for a class of switched systems which are composed of a finite set of continuoustime linear subsystems with norm bounded uncertainties. Under the assumption that there is no single quadratically stable subsystem, if a convex combination of subsystems is quadratically stable, then we propose a state-dependent switching law, based on the convex combination of subsystems, such that the entire switched linear system is quadratically stable. When the state information is not available, we extend the discussion to designing an outputdependent switching law by constructing a robust Luenberger observer for each subsystem.
文摘Since September 2011,A 2/O-MBR wastewater treatment plant in Xi'an Siyuan University has been successfully running without replacing any of membrane modules.A total of 6.661 million m^3 of campus wastewater has been treated,and 4.405 million m^3 of water reaching the national urban miscellaneous water standard has been reclaimed and reused.A total of 25 km pipeline,5 pits,scenery fountains,lakes,and 12 pump stations have been constructed for flushing toilets,irrigating green grass lawn and afforest,and cleaning hardened pavement.The design and construction of 5 pits,scenery fountains,and lakes are important to meet the national urban miscellaneous water standard under occasional phosphorus and/or nitrogen exceed concentration.The unit water cost is 4.19 yuan/m^3,including membrane modules depreciation and amortization.After the A 2/O-MBR system passes the membrane modules depreciation and amortization period,the unit water cost is 2.82 yuan/m^3.The water productivity of the membrane stack rises first at the beginning of operation,reaches the maximum value,and then decreases.The average annual transmembrane pressure difference increases by 1.12 kPa.The average VMD of industrial permeability decreases annually by 0.45 m^3.
基金funded by the undergraduate student research training program of the Ministry of Education, the National Natural Science Foundation of China (Grants Nos. 41771495, 41830641, and 41988101)the Second Tibetan Plateau Scientific Expedition and Research Program Grant 2019QZKK0208+1 种基金funded by the European Research Council Synergy project “Imbalance-P ” (Grant No. ERC-2013-Sy G-610028)the European Union’s Horizon 2020 research and innovation project “CONSTRAIN” (Grant No. 820829)
文摘Individual countries are requested to submit nationally determined contributions(NDCs)to alleviate global warming in the Paris Agreement.However,the global climate effects and regional contributions are not explicitly considered in the countries’decision-making process.In this study,we evaluate the global temperature slowdown of the NDC scenario(ΔT=0.6°C)and attribute the global temperature slowdown to certain regions of the world with a compact earth system model.Considering reductions in CO_(2),CH_(4),N_(2)O,BC,and SO_(2),the R5OECD(the Organization for Economic Co-operation and Development in 1990)and R5ASIA(Asian countries)are the top two contributors to global warming mitigation,accounting for 39.3%and 36.8%,respectively.R5LAM(Latin America and the Caribbean)and R5MAF(the Middle East and Africa)followed behind,with contributions of 11.5%and 8.9%,respectively.The remaining 3.5%is attributed to R5REF(the Reforming Economies).Carbon Dioxide emission reduction is the decisive factor of regional contributions,but not the only one.Other greenhouse gases are also important,especially for R5MAF.The contribution of short-lived aerosols is small but significant,notably SO_(2)reduction in R5ASIA.We argue that additional species beyond CO_(2)need to be considered,including short-lived pollutants,when planning a route to mitigate climate change.It needs to be emphasized that there is still a gap to achieve the Paris Agreement 2-degree target with current NDC efforts,let alone the ambitious 1.5-degree target.All countries need to pursue stricter reduction policies for a more sustainable world.
基金This work was supported by the NNSFC (No. 29972017).
文摘From the roots of Ligularia macrophylla, a bisesquiterpene, ligumacrophyllal was isolated and its structure was elucidated on the basis of spectroscopic methods.
文摘A new bisabolane sesquiterpene, 5 beta-acetoxy-4 beta, 8-diangeloyloxy-2 beta,3 beta, :10,11-diepoxy-bisabola-7 (14)-ene, was isolated from the roots of Ligularia songarica and its structure was elucidated on the basis of spectroscopic methods, especially 2D-NMR techniques.
基金Project supported by the National Natural Science Foundation of China(Grant No.11874337).
文摘We study the behaviors of three-dimensional double and triple Weyl fermions in the presence of weak random potential.By performing the Wilsonian renormalization group(RG)analysis,we reveal that the quasiparticle experiences strong renormalization which leads to the modification of the density of states and quasiparticle residue.We further utilize the RG analysis to calculate the classical conductivity and show that the diffusive transport is substantially corrected due to the novel behavior of the quasiparticle and can be directly measured by experiments.
文摘BACKGROUND Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of drugs for treating renal anemia.It is a second-generation hypoxia-inducible factor prolyl hydroxylase-2(PHD2)inhibitor.Roxadustat can effectively increase hemoglobin in patients with dialysis-dependent chronic kidney disease,with an adverse events profile comparable to that of epoetin alfa.We administered roxadustat to a maintenance hemodialysis patient who was allergic to erythropoiesis-stimulating agents(ESAs)and depended on blood transfusion for five years.After applying Roxadustat,the patient’s anemia improved significantly.CASE SUMMARY A 77-year-old Chinese man had type 2 diabetes for 16 years,underwent maintenance hemodialysis for five years,and had fatigue for five years.Laboratory tests showed severe anemia(hemoglobin concentration of 42 g/L).The patient was administered a subcutaneous injection of ESAs before dialysis.He suffered an allergic shock immediately and fainted.His blood pressure dropped to undetectable levels.He was not administered ESAs henceforth.The patient was prescribed iron supplements and received blood transfusions occasionally for five years.His hemoglobin concentration ranged from 42-68 g/L.After taking six weeks of oral roxadustat three times weekly(100 mg TIW),the patient’s hemoglobin concentration increased significantly,and his symptoms decreased.We adjusted the doses of roxadustat,and the hemoglobin concentration was maintained between 97 and 126 g/L.CONCLUSION Oral roxadustat is effective in treating anemia in maintenance hemodialysis patients who cannot be administered ESAs.
基金the National Natural Science Foundation of China(61903129)。
文摘Dear Editor,This letter is concerned with quadratic L_(2) performance(quadratic stability and L_(2) gain)for switched uncertain linear systems(SULS)with norm-bounded uncertainties.Assuming that no single uncertain subsystem achieves quadratic L_(2) performanceγbut a convex combination of the subsystems can make it,we propose a state-dependent switching law such that the SULS achieves the desired quadratic L_(2) performance.The discussion is extended to the SULS with state feedback control,and a sufficient condition is proposed to design the state feedback gains and the switching law simultaneously.
基金Supported by the the National Natural Science Foundation of China(Grant No.11874337)。
文摘We report an exact numerical study on disorder effect in double-Weyl semimetals,and compare exact numerical solutions for the quasiparticle behavior with the Born approximation and renormalization group results.It is revealed that the low-energy quasiparticle properties are renormalized by multiple-impurity scattering processes,leading to apparent power-law behavior of the self-energy.Therefore,the quasiparticle residue surrounding nodal points is considerably reduced and vanishes as ZE∝Er with nonuniversal exponent.We show that such unusual behavior of the quasiparticle leads to strong temperature dependence of diffusive conductivity.Remarkably,we also find a universal minimum conductivity along the direction of linear dispersion at the nodal point,which can be directly observed by experimentalist.
文摘AIM：To identify the effects of interleukin（IL）-13 on retinal pigment epithelial（RPE） cells and the IL-13 level in aqueous humor of age-related macular degeneration（AMD） patients.METHODS：IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay（ELISA）.ARPE-19 cells were treated with 10 ng/m L IL-13 for 12,24,and 48 h.The cell proliferaton was evaluated by the MTS method.The m RNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction（q RT-PCR） and Western blot respectively.The expression of tumor necrosis factor-α（TNF-α）,transforming growth factor-β（TGF-β） and vascular endothelial growth factor（VEGF） were assessed by ELISA.RESU LTS：IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control（167.33±17.64 vs 27.12±5.65 pg/m L;P〈0.01）.In vit ro,IL-13 of high concentrations（10,15,and 20 ng/m L） inhibited ARPE-19 cell proliferation.α-SMA m RNA in ARPE-19 cell were increased（1.017±0.112 vs 1.476±0.168;P〈0.001） and ZO-1 decreased（1.051±0.136 vs 0.702±0.069;P〈0.001） after treated with 10 ng/m L IL-13 for 48 h.The protein expression of α-SMA and ZO-1 also showed the same tendency（α-SMA：P=0.038;ZO-1：P=0.008）.IL-13 significantly reduced the level of TNF-α（44.70±1.67 vs 31.79±3.53 pg/m L;P=0.005） at 48 h,but the le vel of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/m L at 24h（P=0.004） and from 61.26±1.11 to 86.91±3.59 pg/m L at 48h（P〈0.001）.While expressions of VEGF didn＇t change after IL-13 treatment.CONCLUSION：IL-13 in vitr o inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.
文摘BACKGROUND:Experimental autoimmune myasthenia gravis(EAMG)and anti-AchR antibody of human myasthenia gravis are the same immune globulin.This antibody restricts the activity of nicotinic acetylcholine receptor and the amount of receptor binding sites is decreased,so myasthenia gravis occurs.OBJECTIVE:To observe the therapeutic effect and mechanism of action of Qiangjijianli capsule on EAMG rats.DESIGN:A randomized controlled animal experiment.SETTING:Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine.MATERIALS:Acetylcholine receptors(AchR)were extracted from electric skate's electric organ which lives in the sea near Guangzhou.It had high biological activity and the protein content was 1.63 g/L.Qiangjijianli capsule(Astragalus mongholicus,Codonopsis pilosula,Atractylodes macrocephala,Angelica sinensis,Bupleurum chinense,Cairo morningglory root or leaf,Glycyrrhiza uralensis,etc.0.5 g crude drug per capsule)was bought from the Manufacturing Laboratory of Guangzhou University of Traditional Chinese Medicine with the Batch No.89-11-1.METHODS:This experiment was carried out in the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine from May to August 1990.①Adult female SD rats were immunized with AchR.The animals'movement condition was observed and recorded everyday.Ten rats were chosen as normal control group,and they were not given any treatment and raised normally.After modeled,20 successful rats were randomly assigned into 2 groups:treatmental group and model group.2 mL Qiangjijianli capsule suspension(1 g)was intragastrically administrated into each rat of treatmental group for 30 days;The same amount of clean water was intragastrically administrated into the rats of model group for 30 days.②Serum AchR antibody was measured with ABC-ELISA method.After administration,the rats were sacrificed.The complete diaphragmatic muscle was extracted for in vitro receptor binding test.The constitution of N-AchR per milligram of tissue was measured with FT-603 well-typeγscintillation detector and FH408 calibrater.③t test was used for the comparison of difference of mean value of two samples.MAIN OUTCOME MEASURES:The effect of Qiangjijianli capsule on the amount of binding site of serum AchR antibody and nicotine-like acetylcholinergic receptor(N-AChR).RESULTS:Before Qiangjijianli capsule treatment,serum AchR antibody titre was close between model group and treatmental group(0.82±0.15 vs.0.79±0.12,P>0.05);After Qiangjijianli capsule treatment,serum AchR antibody titre of treatmental group was significantly decreased(0.45±0.11,t=6.602,P<0.01),and that in the treatmental group did not change significantly(0.71±0.13,P>0.05).So,serum AchR antibody titre of treatmental group was significantly lower than that of model group(t=5.780,P<0.01).③The number of N-AchR of normal control group was significantly more than that of model group[(1503±156)mg·min-1 vs.(1118±128)mg·min-1,t=6.034,P<0.01].The number of N-AchR of treatmental group was significantly more than that of model group[(1277±143)mg·min^(-1)vs.(1118±128)mg·min^(-1),t=2.619,P<0.05].③After the treatment of Qiangjijianli capsule,all of the six rats which had clinical symptoms in treatmental group did well more or less,while in model group,the six rats had no change except one.CONCLUSION:Qiangjijianli capsule can improve the symptoms of myasthenia gravis by immunological regulation and pharmacological effect of N-AchR.
