The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceu...The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical formulations.In this work,a developed machine-learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular descriptors.Under the few-shot learning framework,thermodynamic theory(perturbed-chain statistical associating fluid theory)was used for data augmentation,and computational chemistry was applied for molecular descriptors'screening.The results showed that the developed machine-learning model can predict the API-polymer phase diagram accurately,broaden the solubility data of APIs in polymers,and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully,which provided efficient guidance for the development of pharmaceutical formulations.展开更多
As a technology of separation and purification,crystallization plays a vital role in diverse industries such as inorganic salt,pharmaceutical,and food industries,which has a huge impact on purity,crystal polymorph,cry...As a technology of separation and purification,crystallization plays a vital role in diverse industries such as inorganic salt,pharmaceutical,and food industries,which has a huge impact on purity,crystal polymorph,crystal morphology,and particle size distribution of final products.In the past few decades,with the rapid advancement of experimental approaches and molecular simulation methods,considerable advances in the interpretation of crystallization mechanisms have been obtained,promoting the investigation and understanding of crystallization theories greatly.In this review,the advances of pharmaceutical crystallization theories in recent years from the perspectives of nucleation and crystal growth are summarized and discussed.Two thermodynamic models that are helpful in the study of the crystallization mechanisms will be introduced.In this section,the perturbed-chain statistical associating fluid theory(PC-SAFT)and a chemical-potential-gradient model will be introduced,which have been successfully applied in pharmaceutical solubility prediction,the research of dissolution mechanism as well as dissolution kinetics analysis.These two models are expected to be applied to the study of pharmaceutical crystallization process and mechanism.Furthermore,molecular simulation based on the interaction between particles can provide structural information,thermodynamics,and dynamics properties of complex systems at the molecular level,like intermolecular interaction and surface adsorption energies.Application and some shortcomings of molecular simulation,especially molecular dynamics simulation,in the field of pharmaceutical crystallization will be expounded.展开更多
Local hydrodynamics of a gas–liquid–solid system,such as bubble circulation regime,gas holdup,liquid velocity and axial profile of solid concentration,are studied in a two-stage internal loop airlift reactor.Empiric...Local hydrodynamics of a gas–liquid–solid system,such as bubble circulation regime,gas holdup,liquid velocity and axial profile of solid concentration,are studied in a two-stage internal loop airlift reactor.Empirical correlations for gas holdup and liquid velocity are proposed to ease the reactor design and scale-up.Different bubble circulation regimes were displayed in the first(lower) and second(upper) stages.Increasing superficial gas velocity and solid loading can promote regime transition of the second stage,and the gas holdup of the second stage is higher than that of the lower stage.In addition,the effects of solid loading on bubble behaviour are experimentally investigated for each stage.It is found that bubble size in the downcomer decreases with the presence of solid particles,and bubble size distribution widens under higher superficial gas velocity and lower solid loading.展开更多
Pore characteristics have been identified as key design parameters for osteoimmunomodulation.The strategy reported here is to create an appropriate immune microenvironment by regulating pore characteristics of scaffol...Pore characteristics have been identified as key design parameters for osteoimmunomodulation.The strategy reported here is to create an appropriate immune microenvironment by regulating pore characteristics of scaffolds,thereby promoting early angiogenesis and enhancing osteogenesis.A series of collagen/nanohydroxyapatite(Col/nHAP)composite scaffolds with ordered lamellar structures and different layer spacings were prepared by mimicking the ordered lamellar topology of the bone matrix.Our research indicated that the layer spacing and ordered topology of the scaffold exerted an important influence on phenotype transformation of macrophages and the secretion of angiogenic factors.The Col/nHAP-O(135)with large layer spacing not only supported cell attachment and diffusion in vitro,but also promoted early angiogenesis by timely switching from M1 to M2 macrophage phenotype.In vivo data showed that the layer spacing and the ordered structure of the scaffold synergistically regulated the inflammatory response and triggered macrophages to secrete more angiogenesis related cytokines.Col/nHAP-O(135)considerably promoted the neovascularization and new bone formation in the defect site,indicating that Col/nHAPO(135)could significantly enhance the osteogenic activity of stem cells with the involvement of macrophages.展开更多
We experimentally demonstrate two kinds of all few-mode fiber(FMF) ring lasers with high-order mode(HOM)oscillation in the laser cavity. One kind is a switchable-wavelength all-FMF HOM laser with an output of tunable ...We experimentally demonstrate two kinds of all few-mode fiber(FMF) ring lasers with high-order mode(HOM)oscillation in the laser cavity. One kind is a switchable-wavelength all-FMF HOM laser with an output of tunable optical vortex beams(OVBs); the other is a Q-switched all-FMF HOM laser with an output of pulsed cylindrical vector beams(CVBs). The lasers are composed of all-FMF components and few-mode erbium-doped fiber. A Sagnac interferometer made of a 3 dB FMF coupler functions as the wavelength selector, and switchable multiwavelength tunable OVBs are experimentally realized. Carbon nanotube-based saturable absorbers and the nonlinear polarization rotation technique are used to achieve Q-switched CVB lasers. This is the first report, to our knowledge, on the generation of switchable-wavelength and Q-switched HOM beams in all-FMF laser cavities.展开更多
China＇s recent removal of the last ceiling restriction on deposit rates in October 2015 is a milestone in interest rate liberalization, but not the end of it. International experience suggests that, without structura...China＇s recent removal of the last ceiling restriction on deposit rates in October 2015 is a milestone in interest rate liberalization, but not the end of it. International experience suggests that, without structural and quantitative reforms, simply freeing interest rates can result in major financial stress. Before China＇s central bank can completely relinquish implicit or explicit guidance for commercial banks interest rate determination, it needs to accomplish two tasks： improvement of commercial banks＇ pricing capability as well as the monetary policy transmission mechanism. Both tasks require significant reform measures to be initiated, such as enforcing market discipline, forming a new monetary policy framework, developing money and capital markets, abandoning quantitative restrictions on credit and reforming the financial regulatory system.展开更多
The advance of cryptocurrencies has sparked wide concern over their interplay with the existing global financial market.This paper analyzes the risk spillover relation between cryptocurrencies and major financial asse...The advance of cryptocurrencies has sparked wide concern over their interplay with the existing global financial market.This paper analyzes the risk spillover relation between cryptocurrencies and major financial assets,and unravels how cryptocurrencies could influence global financial systemic risk.We find that cryptocurrencies function as a separate risk source from traditional assets.Major legislative,financial and technological events in the cryptocurrency market may affect risk spillover dynamics.Although the overall penetration of cryptocurrencies is not yet deep,introducing cryptocurrency can significantly increase the systemic risk to traditional markets during low risk level episodes.展开更多
Economists have put forward various proposals to deal with the growing risks of the global reserve currency system. In this paper we recommend that Asian economies hold each other＇s currencies as part of their foreig...Economists have put forward various proposals to deal with the growing risks of the global reserve currency system. In this paper we recommend that Asian economies hold each other＇s currencies as part of their foreign reserves. Different from crisis-fighting currency swap arrangements or crisis-rescuing fund mechanisms, this mechanism means that reserves wouM be held, with a regular arrangement in place and on an ongoing basis. We propose that the global reserve system shouM be pushed in the direction of diversification, which could be a transitional step toward a new single reserve system. This mechanism would not necessitate any currency being a globally accepted reserve currency but would mean that every currency carried some weight in the reserve system. Establishment of such a system would require significant development of regional bond markets and facilitation of macroeconomic surveillance among the economies.展开更多
Papillon-Lefevre Syndrome is a rare autosomal recessive disorder characterized by rapidly progressive periodontitis and confined palrnoplantar hyperkeratosis resulting from genetic mutations in cathepsin C （CTSC）. T...Papillon-Lefevre Syndrome is a rare autosomal recessive disorder characterized by rapidly progressive periodontitis and confined palrnoplantar hyperkeratosis resulting from genetic mutations in cathepsin C （CTSC）. The present study investigated the effect of CTSC on keratinocyte proliferation and apoptosis. HaCaT keratinocytes were transfected with wild-type CTSC and CTSC-targeted siRNAs to investigate the effects of CTSC expression on cell keratosis. Real-time PCR and Western blot analyses showed that the levels of loricrin and keratin （KRT）-I, but not KRT9, was correlated with CTSC expression. Loricrin was increased in the CTSC-overex- pression group and downregulated in the CTSC-silenced group. A positive association between loricrin expression and cell apoptosis was detected in HaCaT keratinocytes. KRT1 was decreased in the CTSC-overexpression group and increased in the CTSC-silenced group. Prominent, punctuate KRT1 aggregates were present in CTSC-knockdown HaCaT cells. This study suggested that loss of CTSC contributes to keratinocyte hyperkeratosis via downregulation of loricrin and enhanced cell proliferation.展开更多
China has been at the forefront of financial technology(fintech)growth,especially in areas of digital financial inclusion,such as providing mobile payment,online lending and digital insurance to small and medium-sized...China has been at the forefront of financial technology(fintech)growth,especially in areas of digital financial inclusion,such as providing mobile payment,online lending and digital insurance to small and medium-sized enterprises(SMEs)and low-income individuals.Each of the two main mobile payment service providers,WeChat Pay and Alipay,has close to one billion users.During the first 10 months of 2018,China made a record US$12.8tn in mobile payment transactions,surpassing the US$49.3bn transactions made in the US.展开更多
基金the financial support from the National Natural Science Foundation of China(22278070,21978047,21776046)。
文摘The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical formulations.In this work,a developed machine-learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular descriptors.Under the few-shot learning framework,thermodynamic theory(perturbed-chain statistical associating fluid theory)was used for data augmentation,and computational chemistry was applied for molecular descriptors'screening.The results showed that the developed machine-learning model can predict the API-polymer phase diagram accurately,broaden the solubility data of APIs in polymers,and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully,which provided efficient guidance for the development of pharmaceutical formulations.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.21776046 and 21606043)the Six Talent Peaks Project in Jiangsu Province(Grant No.XCL-079)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.2242019K40145)the Recruitment Program for Young Professionals(the Thousand Youth Talents Plan)。
文摘As a technology of separation and purification,crystallization plays a vital role in diverse industries such as inorganic salt,pharmaceutical,and food industries,which has a huge impact on purity,crystal polymorph,crystal morphology,and particle size distribution of final products.In the past few decades,with the rapid advancement of experimental approaches and molecular simulation methods,considerable advances in the interpretation of crystallization mechanisms have been obtained,promoting the investigation and understanding of crystallization theories greatly.In this review,the advances of pharmaceutical crystallization theories in recent years from the perspectives of nucleation and crystal growth are summarized and discussed.Two thermodynamic models that are helpful in the study of the crystallization mechanisms will be introduced.In this section,the perturbed-chain statistical associating fluid theory(PC-SAFT)and a chemical-potential-gradient model will be introduced,which have been successfully applied in pharmaceutical solubility prediction,the research of dissolution mechanism as well as dissolution kinetics analysis.These two models are expected to be applied to the study of pharmaceutical crystallization process and mechanism.Furthermore,molecular simulation based on the interaction between particles can provide structural information,thermodynamics,and dynamics properties of complex systems at the molecular level,like intermolecular interaction and surface adsorption energies.Application and some shortcomings of molecular simulation,especially molecular dynamics simulation,in the field of pharmaceutical crystallization will be expounded.
基金Supported by the State Key Laboratory of Chemical Engineering(SKL-ChE-16B01)China Postdoctoral Science Foundation(2016M601263)
文摘Local hydrodynamics of a gas–liquid–solid system,such as bubble circulation regime,gas holdup,liquid velocity and axial profile of solid concentration,are studied in a two-stage internal loop airlift reactor.Empirical correlations for gas holdup and liquid velocity are proposed to ease the reactor design and scale-up.Different bubble circulation regimes were displayed in the first(lower) and second(upper) stages.Increasing superficial gas velocity and solid loading can promote regime transition of the second stage,and the gas holdup of the second stage is higher than that of the lower stage.In addition,the effects of solid loading on bubble behaviour are experimentally investigated for each stage.It is found that bubble size in the downcomer decreases with the presence of solid particles,and bubble size distribution widens under higher superficial gas velocity and lower solid loading.
基金the National Natural Science Foundation of China(No.31971270)the grant of Peak Climbing Project of Foshan Hospital of Traditional Chinese Medicine(CN)(No.202000190).
文摘Pore characteristics have been identified as key design parameters for osteoimmunomodulation.The strategy reported here is to create an appropriate immune microenvironment by regulating pore characteristics of scaffolds,thereby promoting early angiogenesis and enhancing osteogenesis.A series of collagen/nanohydroxyapatite(Col/nHAP)composite scaffolds with ordered lamellar structures and different layer spacings were prepared by mimicking the ordered lamellar topology of the bone matrix.Our research indicated that the layer spacing and ordered topology of the scaffold exerted an important influence on phenotype transformation of macrophages and the secretion of angiogenic factors.The Col/nHAP-O(135)with large layer spacing not only supported cell attachment and diffusion in vitro,but also promoted early angiogenesis by timely switching from M1 to M2 macrophage phenotype.In vivo data showed that the layer spacing and the ordered structure of the scaffold synergistically regulated the inflammatory response and triggered macrophages to secrete more angiogenesis related cytokines.Col/nHAP-O(135)considerably promoted the neovascularization and new bone formation in the defect site,indicating that Col/nHAPO(135)could significantly enhance the osteogenic activity of stem cells with the involvement of macrophages.
基金National Natural Science Foundation of China(NSFC)(61635006,91750108,61520106014)Science and Technology Commission of Shanghai Municipality(STCSM)(16520720900)
文摘We experimentally demonstrate two kinds of all few-mode fiber(FMF) ring lasers with high-order mode(HOM)oscillation in the laser cavity. One kind is a switchable-wavelength all-FMF HOM laser with an output of tunable optical vortex beams(OVBs); the other is a Q-switched all-FMF HOM laser with an output of pulsed cylindrical vector beams(CVBs). The lasers are composed of all-FMF components and few-mode erbium-doped fiber. A Sagnac interferometer made of a 3 dB FMF coupler functions as the wavelength selector, and switchable multiwavelength tunable OVBs are experimentally realized. Carbon nanotube-based saturable absorbers and the nonlinear polarization rotation technique are used to achieve Q-switched CVB lasers. This is the first report, to our knowledge, on the generation of switchable-wavelength and Q-switched HOM beams in all-FMF laser cavities.
文摘China＇s recent removal of the last ceiling restriction on deposit rates in October 2015 is a milestone in interest rate liberalization, but not the end of it. International experience suggests that, without structural and quantitative reforms, simply freeing interest rates can result in major financial stress. Before China＇s central bank can completely relinquish implicit or explicit guidance for commercial banks interest rate determination, it needs to accomplish two tasks： improvement of commercial banks＇ pricing capability as well as the monetary policy transmission mechanism. Both tasks require significant reform measures to be initiated, such as enforcing market discipline, forming a new monetary policy framework, developing money and capital markets, abandoning quantitative restrictions on credit and reforming the financial regulatory system.
基金This work was supported by the National Social Science Fund Major Project of China(No.18ZDA091),the Swiss National Science Foundation(No.100018_176387/1)and the Peking University Institute of Digital Finance Project.
文摘The advance of cryptocurrencies has sparked wide concern over their interplay with the existing global financial market.This paper analyzes the risk spillover relation between cryptocurrencies and major financial assets,and unravels how cryptocurrencies could influence global financial systemic risk.We find that cryptocurrencies function as a separate risk source from traditional assets.Major legislative,financial and technological events in the cryptocurrency market may affect risk spillover dynamics.Although the overall penetration of cryptocurrencies is not yet deep,introducing cryptocurrency can significantly increase the systemic risk to traditional markets during low risk level episodes.
文摘Economists have put forward various proposals to deal with the growing risks of the global reserve currency system. In this paper we recommend that Asian economies hold each other＇s currencies as part of their foreign reserves. Different from crisis-fighting currency swap arrangements or crisis-rescuing fund mechanisms, this mechanism means that reserves wouM be held, with a regular arrangement in place and on an ongoing basis. We propose that the global reserve system shouM be pushed in the direction of diversification, which could be a transitional step toward a new single reserve system. This mechanism would not necessitate any currency being a globally accepted reserve currency but would mean that every currency carried some weight in the reserve system. Establishment of such a system would require significant development of regional bond markets and facilitation of macroeconomic surveillance among the economies.
文摘Papillon-Lefevre Syndrome is a rare autosomal recessive disorder characterized by rapidly progressive periodontitis and confined palrnoplantar hyperkeratosis resulting from genetic mutations in cathepsin C （CTSC）. The present study investigated the effect of CTSC on keratinocyte proliferation and apoptosis. HaCaT keratinocytes were transfected with wild-type CTSC and CTSC-targeted siRNAs to investigate the effects of CTSC expression on cell keratosis. Real-time PCR and Western blot analyses showed that the levels of loricrin and keratin （KRT）-I, but not KRT9, was correlated with CTSC expression. Loricrin was increased in the CTSC-overex- pression group and downregulated in the CTSC-silenced group. A positive association between loricrin expression and cell apoptosis was detected in HaCaT keratinocytes. KRT1 was decreased in the CTSC-overexpression group and increased in the CTSC-silenced group. Prominent, punctuate KRT1 aggregates were present in CTSC-knockdown HaCaT cells. This study suggested that loss of CTSC contributes to keratinocyte hyperkeratosis via downregulation of loricrin and enhanced cell proliferation.
文摘China has been at the forefront of financial technology(fintech)growth,especially in areas of digital financial inclusion,such as providing mobile payment,online lending and digital insurance to small and medium-sized enterprises(SMEs)and low-income individuals.Each of the two main mobile payment service providers,WeChat Pay and Alipay,has close to one billion users.During the first 10 months of 2018,China made a record US$12.8tn in mobile payment transactions,surpassing the US$49.3bn transactions made in the US.
