Memristors as non-volatile memory devices have gained numerous attentions owing to their advantages in storage,in-memory computing, synaptic applications, etc. In recent years, two-dimensional(2D) materials with moder...Memristors as non-volatile memory devices have gained numerous attentions owing to their advantages in storage,in-memory computing, synaptic applications, etc. In recent years, two-dimensional(2D) materials with moderate defects have been discovered to exist memristive feature. However, it is very difficult to obtain moderate defect degree in 2D materials, and studied on modulation means and mechanism becomes urgent and essential. In this work, we realized memristive feature with a bipolar switching and a configurable on/off ratio in a two-terminal MoS_(2) device(on/off ratio ~100), for the first time, from absent to present using laser-modulation to few-layer defect-free MoS_(2)(about 10 layers), and its retention time in both high resistance state and low resistance state can reach 2×10^(4) s. The mechanism of the laser-induced memristive feature has been cleared by dynamic Monte Carlo simulations and first-principles calculations. Furthermore, we verified the universality of the laser-modulation by investigating other 2D materials of TMDs. Our work will open a route to modulate and optimize the performance of 2D semiconductor memristive devices.展开更多
Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumo...Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.展开更多
How to trigger strong anti-tumor immune responses has become a focus for tumor therapy.Here,we report the human-induced pluripotent stem cells(iPSs)to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodyna...How to trigger strong anti-tumor immune responses has become a focus for tumor therapy.Here,we report the human-induced pluripotent stem cells(iPSs)to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy(PDT)and enhanced immunotherapy.Ce6 photosensitizer was attached on manganese dioxide(MnO2)nanoparticles,and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes.The iPS-MnO2@Ce6 actively targeted in vivo tumors,the acidic microenvironment triggered interaction between MnO2 and H2O2,released large quantities of oxygen,alleviated hypoxia in tumor.Upon PDT,singlet oxygen formed,broken iPSs released tumor-shared antigens,which evoked an intensive innate and adaptive immune response against the tumor,improving dendritic cells matured,effector T cells,and natural killer cells were activated.Meanwhile,regulatory T cells were reduced,and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6(P<0.05).The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor.Human iPS s loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.展开更多
Idiopathic pulmonary fibrosis (IPF) is characterized by exuberant apoptosis and inadequate regeneration of lung parenchyma cells. Intratracheal alveolar type II epithelial cell instillation alleviates lung inflammatio...Idiopathic pulmonary fibrosis (IPF) is characterized by exuberant apoptosis and inadequate regeneration of lung parenchyma cells. Intratracheal alveolar type II epithelial cell instillation alleviates lung inflammation and fibrosis. Resident lung epithelial stem cells, as well as exogenous mesenchymal stem cells, are capable of differentiating into lung epithelial cells and repair the injured lung. It is thus supposed that, either engraftment of exogenous stem cells, or methods facilitating endogenous lung stem cell proliferation, are promising treatments for IPF, a devastating disease. Arrays of cellular and animal studies have shown the potential of stem cells in alleviating experimental lung fibrosis. Moreover, clinical trials have been launched to investigate the potentials of cell-based therapy in IPF patients. We intend to discuss the newest advances on stem cell therapy in pulmonary fibrosis, particularly the advantages, promises, and possible hurdles to pass from the successes in laboratory experiments to the eventual clinical applications.展开更多
Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin...Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.展开更多
Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for...Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.展开更多
In this paper we study the competitive order timing decisions of two manufacturers with demand forecasting updating and uncertain raw material price.Manufacturers can order the raw materials early when the market is h...In this paper we study the competitive order timing decisions of two manufacturers with demand forecasting updating and uncertain raw material price.Manufacturers can order the raw materials early when the market is highly uncertain with a fixed wholesale price(Contract procurement)or late when the market is less uncertain with an uncertain raw material price(Spot trading).Different from most existing literature,we assume the spot price and the market demand is correlated.We find that in the monopoly setting the manufacturer prefers the contract procurement to the spot trading when the unit wholesale price for the contract procurement is not greater than the expected unit spot price of the raw material.In the duopoly setting,we characterize the equilibria of a strategic order timing game in which manufacturers choose when to buy the raw materials.We find that when the demand during the contract procurement stage and the spot price uncertainty is small both manufacturers prefer the contract procurement strategy and when the demand during the contract procurement stage and the spot price uncertainty is large both manufacturers prefer the spot trading.When the demand during the contract procurement stage and the spot price uncertainty is high and purchase costs do not decline too severely over time,the unique equilibrium of this game is that one manufacturer chooses contract procurement to order early and the other chooses spot trading to order late.Further,we find that the correlation of spot purchasing price and the market demand signal during the contract procurement stage will weaken the advantages of spot trading strategy.When the spot purchasing price and the market demand signal during the contract procurement stage are not correlated,manufacturers prefer spot trading under the highly volatile spot trading price,fluctuating demand,and high information precision.展开更多
In this study, we investigate the association between financial reporting quality and a firm's deviation from its optimal capital structure. We find that a firm's deviation from its optimal capital structure is decr...In this study, we investigate the association between financial reporting quality and a firm's deviation from its optimal capital structure. We find that a firm's deviation from its optimal capital structure is decreasing in financial reporting quality. The results suggest that high-quality financial reporting helps to reduce a firm's deviation from its optimal capital structure. In addition, we document that the relationship is intensified in non-SOEs, in which financial reporting quality plays a more crucial role. Furthermore, we find that bank connections diminish the role of financial reporting quality in optimal capital structure. Our results hold when we control for potential endogeneity in financial reporting quality and capital structure decisions. Our study contributes to both financial reporting quality and capital structure literature. We also contribute to the literature on informal contracts in organizational decision-making.展开更多
For metal nanofilms composed of nanocrystals,the multiple deformation mechanisms will coexist and bring unique and complex elastic-plastic and fracture mechanical properties.By successfully fabricating large quantitie...For metal nanofilms composed of nanocrystals,the multiple deformation mechanisms will coexist and bring unique and complex elastic-plastic and fracture mechanical properties.By successfully fabricating large quantities of uniform doubly-clamped suspended gold(Au)nanobeams with different thicknesses and nanograin sizes,we obtain full-spectrum mechanical features with statistical significance by combining atomic force microscopy(AFM)nanoindentation experiments,nonlinear theoretical model,and numerical simulations.The yield and breaking strengths of the Au nanobeams have a huge increase by nearly an order of magnitude compared with bulk Au and exhibit strong nonlinear effects,and the corresponding strong-yield ratio is up to 4,demonstrating extremely high strength reserve and vibration resistance.The strong-yield ratio gradually decreases with decreasing thickness,identifying a conversion of the failure type from ductile to brittle.Interestingly,the Hall–Petch relationship has been identified to be still valid at the nanoscale,and K in the equation reaches 4.8 Gpa·nm1/2,nearly twice of bulk nanocrystalline Au,which is ascribed to the coupling effect of nanocrystals and nanoscale thickness.展开更多
Surface lattice resonance(SLR)is a pretty effective mechanism to realize ultranarrow linewidths in the spectrum.Herein,we propose and demonstrate reflection-type SLRs in all-metal metasurfaces experimentally,compared ...Surface lattice resonance(SLR)is a pretty effective mechanism to realize ultranarrow linewidths in the spectrum.Herein,we propose and demonstrate reflection-type SLRs in all-metal metasurfaces experimentally,compared with the traditional transmission-type SLR,which can avoid the refractive index(RI)mismatch problem and are more suitable for high-efficiency RI sensing due to direct contact and strong light–matter interaction.The measured SLR linewidth is 13.5 nm influenced by the meta-atom size,which needs a compromise design to keep a balance between the narrow linewidth and noise immunity.Notably,the SLR sensitivity is determined by the lattice period along the polarization direction with regularity,which establishes an intuitive link between structures and optical responses and provides a theoretical guide for metasurface designs.Additionally,incident angle multiplexing will make the resonance wavelength red shift or blue shift in the case of orthogonal polarization.The rectangular array metasurface can realize dual SLRs with different sensing performances.Flexibly,the SLR can also be formed by the different meta-atoms and arrays.This research supports SLR multifarious applications involving not only RI sensing but also nonlinear optics,nano-lasers,etc.展开更多
Many ocean transportation hub systems consist of two container ports that share the container handling business in the area. The container flow passing through a port is the main measurement of the port's competitive...Many ocean transportation hub systems consist of two container ports that share the container handling business in the area. The container flow passing through a port is the main measurement of the port's competitiveness. In this paper we adopt a Hotelling model to study the container port competition in a so-called "dual gateway-port system". The system contains two ports and two terminals, one belonging to each port. The two governments in which the two ports are located compete on cargo fees and the two terminals determine service price and service quality. We study two models with different levels of competition between the terminals. In the ftrst model, the two terminals are owned by two different operators and in the second model, the two terminals are centralized under one operator. The second model exists in practice but is not well studied in the literature. We derive the cargo fee, terminal service price, and service quality equilibria for these two models. We investigate the competition outcome sensitivity with a numerical study. The numerical results reveal that governments prefer terminals to compete with each other. If the terminals do not have competitive advantages in their service quality, then terminal centralization brings more profits to the terminal operator than the competition case.展开更多
In this study,three-dimensional microspherical CQDs/Bi_(2)MoO_(6)heterostructures were synthesized using a simple alcohol-thermal method.It was found that the CQDs/Bi_(2)MoO_(6)had a large specific surface area of 56....In this study,three-dimensional microspherical CQDs/Bi_(2)MoO_(6)heterostructures were synthesized using a simple alcohol-thermal method.It was found that the CQDs/Bi_(2)MoO_(6)had a large specific surface area of 56.0 m^(2)/g,and the introduction of CQDs extended the light absorption spectrum from 480 nm to 496 nm.When utilizing the synthesized CQDs/Bi_(2)MoO_(6)composite for photocatalytic degradation of antibiotic nor-floxacin in a water environment,complete decay of norfloxacin and effective removal of total organic car-bon(TOC)were achieved within 30 min.Through the optimization of material synthesis and experimen-tal conditions,the optimal CQDs loading amount was determined as 200μL,the optimal CQDs/Bi_(2)MoO_(6)dosage was 0.8 g/L.Moreover,the CQDs/Bi_(2)MoO_(6)worked well under a wide pH range of 4.4-10.8.The co-existence of HCO_(3)−enhanced the norfloxacin decay,while the presence of Cl^(−),NO_(3)^(−),and SO_(4)^(2−)slightly retarded it.The synthesized CQDs/Bi_(2)MoO_(6)had the great potential in removing and mineralizing nor-floxacin in real aquatic environments.展开更多
Entanglement plays a vital role in quantum information processing.Owing to its unique material properties,silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum i...Entanglement plays a vital role in quantum information processing.Owing to its unique material properties,silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum information processing capabilities.To date,however,only entanglement of nuclear spins has been reported in silicon carbide,while an entangled photon source,whether it is based on bulk or chip-scale technologies,has remained elusive.Here,we report the demonstration of an entangled photon source in an integrated silicon carbide platform for the first time.Specifically,strongly correlated photon pairs are efficiently generated at the telecom C-band wavelength through implementing spontaneous four-wave mixing in a compact microring resonator in the 4H-silicon-carbide-on-insulator platform.The maximum coincidence-to-accidental ratio exceeds 600 at a pump power of 0.17 mW,corresponding to a pair generation rate of(9±1)×10^(3) pairs/s.Energy-time entanglement is created and verified for such signal-idler photon pairs,with the two-photon interference fringes exhibiting a visibility larger than 99%.The heralded single-photon properties are also measured,with the heralded g^((2))(0)on the order of 10^(−3),demonstrating the SiC platform as a prospective fully integrated,complementary metal-oxide-semiconductor compatible single-photon source for quantum applications.展开更多
基金supported by the National Natural Science Foundation of China(Nos.51971070,10974037,and 62205011)the National Key Research and Development Program of China(No.2016YFA0200403)+6 种基金Eu-FP7 Project(No.247644)CAS Strategy Pilot Program(No.XDA 09020300)Fundamental Research Funds for the Central Universities(No.buctrc202122)the Open Research Project of Zhejiang province Key Laboratory of Quantum Technology and Device(No.20220401)the Open Research Project of Special Display and Imaging Technology Innovation Center of Anhui Province(No.2022AJ05001)funded by the Ph.D Foundation of Hebei University of Water Resources and Electric Engineering(No.SYBJ2202)Funded by Science and Technology Project of Hebei Education Department(No.BJK2022027)。
文摘Memristors as non-volatile memory devices have gained numerous attentions owing to their advantages in storage,in-memory computing, synaptic applications, etc. In recent years, two-dimensional(2D) materials with moderate defects have been discovered to exist memristive feature. However, it is very difficult to obtain moderate defect degree in 2D materials, and studied on modulation means and mechanism becomes urgent and essential. In this work, we realized memristive feature with a bipolar switching and a configurable on/off ratio in a two-terminal MoS_(2) device(on/off ratio ~100), for the first time, from absent to present using laser-modulation to few-layer defect-free MoS_(2)(about 10 layers), and its retention time in both high resistance state and low resistance state can reach 2×10^(4) s. The mechanism of the laser-induced memristive feature has been cleared by dynamic Monte Carlo simulations and first-principles calculations. Furthermore, we verified the universality of the laser-modulation by investigating other 2D materials of TMDs. Our work will open a route to modulate and optimize the performance of 2D semiconductor memristive devices.
基金supported from 973 Project (Grant No. 2015CB931802 and 2017YFA0205301)Chinese National Natural Scientific Fund (Grant No.81327002 and 81803094)+1 种基金China Postdoctoral Science Foundation (Grant No. 2017M621486)Funding from Shanghai Engineering Research Center for Intelligent diagnosis and treatment instrument (Grant No.15DZ2252000)
文摘Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.
基金financially supported by National Nature Scientific foundation(81803094,81802979 and 81921002)the National Foundational Basic Research Project of China(2017YFA0205301 and 2015CB931802)+3 种基金Shanghai Municipal Commission of Economy and Information Technology Fund(No.XC-ZXSJ-02-2016-05)the medical engineering cross project of Shanghai Jiao Tong university(YG2017ZD05,YG2016ZD10 and YG2017Z D05)the Project of Thousand Youth Talents from Chinathe National Key Research and Development Program of China(2017YFC1200904 and 2017YFE0124400)。
文摘How to trigger strong anti-tumor immune responses has become a focus for tumor therapy.Here,we report the human-induced pluripotent stem cells(iPSs)to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy(PDT)and enhanced immunotherapy.Ce6 photosensitizer was attached on manganese dioxide(MnO2)nanoparticles,and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes.The iPS-MnO2@Ce6 actively targeted in vivo tumors,the acidic microenvironment triggered interaction between MnO2 and H2O2,released large quantities of oxygen,alleviated hypoxia in tumor.Upon PDT,singlet oxygen formed,broken iPSs released tumor-shared antigens,which evoked an intensive innate and adaptive immune response against the tumor,improving dendritic cells matured,effector T cells,and natural killer cells were activated.Meanwhile,regulatory T cells were reduced,and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6(P<0.05).The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor.Human iPS s loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.
文摘Idiopathic pulmonary fibrosis (IPF) is characterized by exuberant apoptosis and inadequate regeneration of lung parenchyma cells. Intratracheal alveolar type II epithelial cell instillation alleviates lung inflammation and fibrosis. Resident lung epithelial stem cells, as well as exogenous mesenchymal stem cells, are capable of differentiating into lung epithelial cells and repair the injured lung. It is thus supposed that, either engraftment of exogenous stem cells, or methods facilitating endogenous lung stem cell proliferation, are promising treatments for IPF, a devastating disease. Arrays of cellular and animal studies have shown the potential of stem cells in alleviating experimental lung fibrosis. Moreover, clinical trials have been launched to investigate the potentials of cell-based therapy in IPF patients. We intend to discuss the newest advances on stem cell therapy in pulmonary fibrosis, particularly the advantages, promises, and possible hurdles to pass from the successes in laboratory experiments to the eventual clinical applications.
基金China National Major Project for New Drug Innovation,Grant/Award Number:2017ZX09304015Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2016-I2M-1-001。
文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.
基金support of the National Basic Research Program of China(Nos.2017YFA0205301 and 2015CB931802)the National Natural Scientific Foundation of China(Nos.81903169,81803094,81602184,81822024,and 81571729)+5 种基金Shanghai Municipal Commission of Economy and Information Technology Fund(No.XC-ZXSJ-02-2016-05)the Medical Engineering Cross Project of Shanghai Jiao Tong university(Nos.YG2016ZD10 and YG2017Z D05)the Project of Thousand Youth Talents from China,and the National Key Research and Development Program of China(No.2017YFC1200904)the financial support of Shanghai Sailing Program(No.19YF1422300)Sponsor from Startup Fund for Yongman Research at SJTU(No.18X100040044)Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument(No.15DZ2252000)are also acknowledged.
文摘Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.
基金the National Natural Science Foundation of China under Grant Nos.71471118,71671040,71871145 and 71822103the Major Project of National Natural Science Foundation of China under Grant Nos.71790615,71991461 and 71991474。
文摘In this paper we study the competitive order timing decisions of two manufacturers with demand forecasting updating and uncertain raw material price.Manufacturers can order the raw materials early when the market is highly uncertain with a fixed wholesale price(Contract procurement)or late when the market is less uncertain with an uncertain raw material price(Spot trading).Different from most existing literature,we assume the spot price and the market demand is correlated.We find that in the monopoly setting the manufacturer prefers the contract procurement to the spot trading when the unit wholesale price for the contract procurement is not greater than the expected unit spot price of the raw material.In the duopoly setting,we characterize the equilibria of a strategic order timing game in which manufacturers choose when to buy the raw materials.We find that when the demand during the contract procurement stage and the spot price uncertainty is small both manufacturers prefer the contract procurement strategy and when the demand during the contract procurement stage and the spot price uncertainty is large both manufacturers prefer the spot trading.When the demand during the contract procurement stage and the spot price uncertainty is high and purchase costs do not decline too severely over time,the unique equilibrium of this game is that one manufacturer chooses contract procurement to order early and the other chooses spot trading to order late.Further,we find that the correlation of spot purchasing price and the market demand signal during the contract procurement stage will weaken the advantages of spot trading strategy.When the spot purchasing price and the market demand signal during the contract procurement stage are not correlated,manufacturers prefer spot trading under the highly volatile spot trading price,fluctuating demand,and high information precision.
文摘In this study, we investigate the association between financial reporting quality and a firm's deviation from its optimal capital structure. We find that a firm's deviation from its optimal capital structure is decreasing in financial reporting quality. The results suggest that high-quality financial reporting helps to reduce a firm's deviation from its optimal capital structure. In addition, we document that the relationship is intensified in non-SOEs, in which financial reporting quality plays a more crucial role. Furthermore, we find that bank connections diminish the role of financial reporting quality in optimal capital structure. Our results hold when we control for potential endogeneity in financial reporting quality and capital structure decisions. Our study contributes to both financial reporting quality and capital structure literature. We also contribute to the literature on informal contracts in organizational decision-making.
基金supported by the National Natural Science Foundation of China(NSFC)(No.51971070)the National Key Research and Development Program of China(No.2016YFA0200403)+1 种基金Eu-FP7 Project(No.247644)CAS Strategy Pilot Program(No.XRA 09020300).
文摘For metal nanofilms composed of nanocrystals,the multiple deformation mechanisms will coexist and bring unique and complex elastic-plastic and fracture mechanical properties.By successfully fabricating large quantities of uniform doubly-clamped suspended gold(Au)nanobeams with different thicknesses and nanograin sizes,we obtain full-spectrum mechanical features with statistical significance by combining atomic force microscopy(AFM)nanoindentation experiments,nonlinear theoretical model,and numerical simulations.The yield and breaking strengths of the Au nanobeams have a huge increase by nearly an order of magnitude compared with bulk Au and exhibit strong nonlinear effects,and the corresponding strong-yield ratio is up to 4,demonstrating extremely high strength reserve and vibration resistance.The strong-yield ratio gradually decreases with decreasing thickness,identifying a conversion of the failure type from ductile to brittle.Interestingly,the Hall–Petch relationship has been identified to be still valid at the nanoscale,and K in the equation reaches 4.8 Gpa·nm1/2,nearly twice of bulk nanocrystalline Au,which is ascribed to the coupling effect of nanocrystals and nanoscale thickness.
基金National Natural Science Foundation of China(61974004,61931018)National Key Research and Development Program of China(2021YFB3200100)。
文摘Surface lattice resonance(SLR)is a pretty effective mechanism to realize ultranarrow linewidths in the spectrum.Herein,we propose and demonstrate reflection-type SLRs in all-metal metasurfaces experimentally,compared with the traditional transmission-type SLR,which can avoid the refractive index(RI)mismatch problem and are more suitable for high-efficiency RI sensing due to direct contact and strong light–matter interaction.The measured SLR linewidth is 13.5 nm influenced by the meta-atom size,which needs a compromise design to keep a balance between the narrow linewidth and noise immunity.Notably,the SLR sensitivity is determined by the lattice period along the polarization direction with regularity,which establishes an intuitive link between structures and optical responses and provides a theoretical guide for metasurface designs.Additionally,incident angle multiplexing will make the resonance wavelength red shift or blue shift in the case of orthogonal polarization.The rectangular array metasurface can realize dual SLRs with different sensing performances.Flexibly,the SLR can also be formed by the different meta-atoms and arrays.This research supports SLR multifarious applications involving not only RI sensing but also nonlinear optics,nano-lasers,etc.
基金The authors appreciate the anonymous referees and the editor for their help to improve the quality of the paper. This paper was partially supported by the National Natural Science Foundation of China, NSFC Nos. 71001073, 71302109, 71471118, the Humanities and Social Sciences Foundation of Ministry of Education of China (No. 14YJC630096), the Distinguished University Young Scholar Program of Guangdong Province (No. Yq2013140), the Fundamental Research Funds for the Central Universities (No. 15JNQM028) and Natural Science Foundation of SZU (Grant Nos. 201422 and 827000074).
文摘Many ocean transportation hub systems consist of two container ports that share the container handling business in the area. The container flow passing through a port is the main measurement of the port's competitiveness. In this paper we adopt a Hotelling model to study the container port competition in a so-called "dual gateway-port system". The system contains two ports and two terminals, one belonging to each port. The two governments in which the two ports are located compete on cargo fees and the two terminals determine service price and service quality. We study two models with different levels of competition between the terminals. In the ftrst model, the two terminals are owned by two different operators and in the second model, the two terminals are centralized under one operator. The second model exists in practice but is not well studied in the literature. We derive the cargo fee, terminal service price, and service quality equilibria for these two models. We investigate the competition outcome sensitivity with a numerical study. The numerical results reveal that governments prefer terminals to compete with each other. If the terminals do not have competitive advantages in their service quality, then terminal centralization brings more profits to the terminal operator than the competition case.
基金funded by the National Science Foundation of China(Nos.42377452,41877481)the Strategic Priority Research Program of the Chinese Academy of Sciences,China(Nos.XDA23010300,XDA23010000)the Opening Fund of Key Laboratory of Aerosol Chemistry and Physics,Institute of Earth Environment,CAS(No.KLACP2002).
文摘In this study,three-dimensional microspherical CQDs/Bi_(2)MoO_(6)heterostructures were synthesized using a simple alcohol-thermal method.It was found that the CQDs/Bi_(2)MoO_(6)had a large specific surface area of 56.0 m^(2)/g,and the introduction of CQDs extended the light absorption spectrum from 480 nm to 496 nm.When utilizing the synthesized CQDs/Bi_(2)MoO_(6)composite for photocatalytic degradation of antibiotic nor-floxacin in a water environment,complete decay of norfloxacin and effective removal of total organic car-bon(TOC)were achieved within 30 min.Through the optimization of material synthesis and experimen-tal conditions,the optimal CQDs loading amount was determined as 200μL,the optimal CQDs/Bi_(2)MoO_(6)dosage was 0.8 g/L.Moreover,the CQDs/Bi_(2)MoO_(6)worked well under a wide pH range of 4.4-10.8.The co-existence of HCO_(3)−enhanced the norfloxacin decay,while the presence of Cl^(−),NO_(3)^(−),and SO_(4)^(2−)slightly retarded it.The synthesized CQDs/Bi_(2)MoO_(6)had the great potential in removing and mineralizing nor-floxacin in real aquatic environments.
基金financial support from the NIST ITL Building the Future program and CMU-NSF (2127499)The CMU team acknowledges the use of Bertucci Nanotechnology Laboratory at Carnegie Mellon University supported by grant BNL-78657879the Materials Characterization Facility supported by grant MCF-677785.
文摘Entanglement plays a vital role in quantum information processing.Owing to its unique material properties,silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum information processing capabilities.To date,however,only entanglement of nuclear spins has been reported in silicon carbide,while an entangled photon source,whether it is based on bulk or chip-scale technologies,has remained elusive.Here,we report the demonstration of an entangled photon source in an integrated silicon carbide platform for the first time.Specifically,strongly correlated photon pairs are efficiently generated at the telecom C-band wavelength through implementing spontaneous four-wave mixing in a compact microring resonator in the 4H-silicon-carbide-on-insulator platform.The maximum coincidence-to-accidental ratio exceeds 600 at a pump power of 0.17 mW,corresponding to a pair generation rate of(9±1)×10^(3) pairs/s.Energy-time entanglement is created and verified for such signal-idler photon pairs,with the two-photon interference fringes exhibiting a visibility larger than 99%.The heralded single-photon properties are also measured,with the heralded g^((2))(0)on the order of 10^(−3),demonstrating the SiC platform as a prospective fully integrated,complementary metal-oxide-semiconductor compatible single-photon source for quantum applications.