Copula functions have been widely used in stochastic simulation and prediction of streamflow.However,existing models are usually limited to single two-dimensional or three-dimensional copulas with the same bivariate b...Copula functions have been widely used in stochastic simulation and prediction of streamflow.However,existing models are usually limited to single two-dimensional or three-dimensional copulas with the same bivariate block for all months.To address this limitation,this study developed a mixed D-vine copula-based conditional quantile model that can capture temporal correlations.This model can generate streamflow by selecting different historical streamflow variables as the conditions for different months and by exploiting the conditional quantile functions of streamflows in different months with mixed D-vine copulas.The up-to-down sequential method,which couples the maximum weight approach with the Akaike information criteria and the maximum likelihood approach,was used to determine the structures of multivariate Dvine copulas.The developed model was used in a case study to synthesize the monthly streamflow at the Tangnaihai hydrological station,the inflow control station of the Longyangxia Reservoir in the Yellow River Basin.The results showed that the developed model outperformed the commonly used bivariate copula model in terms of the performance in simulating the seasonality and interannual variability of streamflow.This model provides useful information for water-related natural hazard risk assessment and integrated water resources management and utilization.展开更多
Micrometric-thin cells(MCs)with alkali vapor atoms have been valuable for research and applications of hyperfine Zeeman splitting and atomic magnetometers under strong magnetic fields.We theoretically and experimental...Micrometric-thin cells(MCs)with alkali vapor atoms have been valuable for research and applications of hyperfine Zeeman splitting and atomic magnetometers under strong magnetic fields.We theoretically and experimentally study the saturated absorption spectra using a 100-μm cesium MC,where the pump and probe beams are linearly polarized with mutually perpendicular polarizations,and the magnetic field is along the pump beam.Because of the distinctive thin chamber of the MC,crossover spectral lines in saturated absorption spectra are largely suppressed leading to clear splittings of hyperfine Zeeman transitions in experiments,and the effect of spatial magnetic field gradient is expected to be reduced.A calculation method is proposed to achieve good agreements between theoretical calculations and experimental results.This method successfully explains the suppression of crossover lines in MCs,as well as the effects of magnetic field direction,propagation and polarization directions of the pump/probe beam on saturated absorption spectrum.The saturated absorption spectrum with suppressed crossover lines is used for laser frequency stabilization,which may provide the potential value of MCs for high spatial resolution strong-field magnetometry with high sensitivity.展开更多
BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat...BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat RA(D2T RA)that was resistant to either a single ABT or a Janus kinase(JAK)inhibitor(Tofacitinib),but improved with a combination of ABT and JAK inhibitor(Baricitinib,BAT).CASE SUMMARY A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab,Etanercept,Adalimumab,and ABT.According to the European League Against Rheumatism definition,the patient was diagnosed with D2T RA.It was then improved with a combination of ABT and a JAK inhibitor BAT.CONCLUSION ABT combined with BAT may be an acceptable strategy for treating D2T RA.展开更多
AIM:To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis.METHODS:Male Sprague-Dawley rats underwent common bile duct ligation(BDL) for 14 d and were treated with Gardenia jasminoide...AIM:To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis.METHODS:Male Sprague-Dawley rats underwent common bile duct ligation(BDL) for 14 d and were treated with Gardenia jasminoides by gavage.The ef-fects of Gardenia jasminoides on liver fibrosis and the detailed molecular mechanisms were also assessed in human hepatic stellate cells(LX-2) in vitro.RESULTS:Treatment with Gardenia jasminoides decreased serum alanine aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,146.6 ± 15 U/L vs 77 ± 6.5 U/L,P = 0.0007) and aspartate aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,188 ± 35.2 U/L vs 128 ± 19 U/L,P = 0.005) as well as hydroxyproline(BDL vs BDL + 100 mg/kg Gardenia jasminoides,438 ± 40.2 μg/g vs 228 ± 10.3 μg/g liver tissue,P = 0.004) after BDL.Furthermore,Gardenia jasminoides significantly reduced liver mRNA and/or protein expression of transforming growth factor β1(TGF-β1),collagen type?Ⅰ?(Col?Ⅰ) and α-smooth muscle actin(α-SMA).Gardenia jasminoides significantly suppressed the upregulation of TGF-β1,Col?Ⅰand α-SMA in LX-2 exposed to recombinant TGF-β1.Moreover,Gardenia jasminoides inhibited TGF-β1-induced Smad2 phosphorylation in LX-2 cells.CONCLUSION:Gardenia jasminoides exerts antifibrotic effects in the liver fibrosis and may represent a novel antifibrotic agent.展开更多
Many terrestrial experiments have been designed to detect domain walls composed of axions or axionlike particles(ALPs), which are promising candidates of dark matter. When the domain wall crosses over the Earth, the p...Many terrestrial experiments have been designed to detect domain walls composed of axions or axionlike particles(ALPs), which are promising candidates of dark matter. When the domain wall crosses over the Earth, the pseudoscalar field of ALPs could couple to the atomic spins. Such exotic spin-dependent couplings can be searched for by monitoring the transient-in-time change of the atomic spin precession frequency in the presence of a magnetic field. We propose here a single-species cesium atomic comagnetometer, which measures the spin precession frequencies of atoms in different ground-state hyperfine levels, to eliminate the common-mode magnetic-field variations and search for the exotic nonmagnetic couplings solely between protons and ALPs. With the single-species atomic comagnetometer, we experimentally rule out the possibility that the decay constant of the linear pseudoscalar couplings of ALPs to protons is fp■ 3.71 ×107 Ge V. The advanced system has the potential to constrain the constant to be fp■ 10.7 × 109 Ge V, promising to improve astrophysical constraint level by at least one order of magnitude. Our system could provide a sensitive detection method for the global network of optical magnetometers to search for exotic physics.展开更多
Objective:To investigate the intervention effect and specific mechanism of Jisheng Shenqi Decoction plus Panax notoginseng and Turmeric on carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Methods:SPF SD rats ...Objective:To investigate the intervention effect and specific mechanism of Jisheng Shenqi Decoction plus Panax notoginseng and Turmeric on carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Methods:SPF SD rats were randomly divided into control group,model group,and Chinese medicine treatment(low,medium and high dose)groups.The model group and Chinese medicine treatment group were given intraperitoneal injection of 40%CCl4 olive oil solution twice a week.A rat model of liver fibrosis was replicated by the method for 8 weeks.After successful modeling,each drug-administered group was gavaged with corresponding drugs,and the control group and model group were gavaged with equal volume of distilled water,once a day,for 4 weeks.After the last intragastric administration,HE staining and Masson staining were used to observe the pathological morphology of liver tissue,and liver function(ALT,AST)was detected;ELISA method was used to determine transforming growth factorβ(TGF-β),angiotensin II(Ang-Ⅱ),chitinase 3-like protein 1(CHI3L1),interleukin-1(IL-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)content;The expression levels of type I,type III collagen(Col-Ⅰ,Col-Ⅲ)and TGF-βmRNA were determined by RT-PCR.Results:①HE and Masson staining showed that a large number of liver cells in the model group were inflamed and necrotic,the collagen fibers in the liver tissue were extensively proliferated,the fibrous septa were interconnected,and the pseudolobules were formed.Compared with the model group,the levels of ALT,AST,TGF-β,Ang-Ⅱ,CHI3L1,IL-1,IL-6 and TNF-αin the traditional Chinese medicine treatment group were decreased,while the levels of Col-Ⅰ,Col-ⅢThe expressions ofⅢand TGF-βmRNA were decreased,and the effect was most obvious in the middle and high dose groups of traditional Chinese medicine(P<0.01).Conclusion:Jisheng Shenqi Decoction combined with Panax notoginseng and Biejia can significantly improve liver fibrosis induced by CCl4 in rats,and its mechanism may be related to the down-regulation of angiotensin-converting enzyme(ACE)-angiotensin II(Ang-II)-angiotensin II receptor 1(AT1R)signaling pathway related gene expression,reducing the level of related cytokines,promoting the degradation of extracellular matrix and so on.展开更多
High-sensitivity radio-frequency optically pumped magnetometers (RF-OPMs), working without cryogenic condition, play a critical role in magnetic field imaging(MFI) at low frequencies(e.g., 100 Hz to 1 MHz). We introdu...High-sensitivity radio-frequency optically pumped magnetometers (RF-OPMs), working without cryogenic condition, play a critical role in magnetic field imaging(MFI) at low frequencies(e.g., 100 Hz to 1 MHz). We introduce the principle of operation and recent developments of RF-OPMs and focus on reviewing the MFI applications in magnetic induction tomography, ultralow-field magnetic resonance imaging, and magnetic particle imaging. For the applications of RF-OPMs, ranging from industrial monitoring to medical imaging and security screening, the unshielded and portable RF-OPMs(and RF-OPM array)techniques are still under the further development for detecting and scanning over the target object for accomplishing the final three-dimensional imaging, and thus extremely require the abilities of active compensation of the ambient magnetic field and sensor miniaturization in the future.展开更多
There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic met...There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).展开更多
A brief overview of vortex-induced vibration(VIV)of circular cylinders is first given as most of VIVstudies have been focused on this particular bluff cross-section.A critical literature review of VIV of bridge decks ...A brief overview of vortex-induced vibration(VIV)of circular cylinders is first given as most of VIVstudies have been focused on this particular bluff cross-section.A critical literature review of VIV of bridge decks thathighlights physical mechanisms central to VIV from a renewed perspective is provided.The discussion focuses on VIVofbridge decks from wind-tunnel experiments,full-scale observations,semi-empirical models and computational fluidsdynamics(CFD)perspectives.Finally,a recently developed reduced order model(ROM)based on truncated Volterraseries is introduced to model VIVof long-span bridges.This model captures successfully salient features of VIVat“lockin”and unlike most phenomenological models offers physical significance of the model kernels.展开更多
A framework was proposed to identify a comprehensive set of aerodynamic admittance functions for bridge decks. The contributions of the cross-spectra between longitudinal and vertical wind velocity components and betw...A framework was proposed to identify a comprehensive set of aerodynamic admittance functions for bridge decks. The contributions of the cross-spectra between longitudinal and vertical wind velocity components and between turbulence components and gust-induced forces were embedded in the identification procedure. To facilitate application of the identified functions in engineering practice, the concept of an equivalent aerodynamic admittance function was introduced and numerically validated. The equivalent aerodynamic admittance functions of a set of streamlined and bluff cross sections were identified experimentally in a wind tunnel. Buffeting analysis of a bridge deck was carried out and the response predicted using the identified aerodynamic admittance functions compared well with the measured response. In addition, a sensitivity analysis was performed to delineate the influence of aerodynamic and structural parameters on the buffeting response, thereby demonstrating the significance of the proposed identification framework.展开更多
Transgenic ruminants are a valuable resource for both animal breeding and biomedical research.The development of transgenic breeding is proceeding slowly,because it suffers from low efficiency of gene transfer and pos...Transgenic ruminants are a valuable resource for both animal breeding and biomedical research.The development of transgenic breeding is proceeding slowly,because it suffers from low efficiency of gene transfer and possible safety problems from uncontrolled random integration.However,new breeding methods combined with genome editing and somatic cell nuclear transfer or microinjection can offer an economic and efficient way to produce gene-edited ruminants,which can serve as bioreactors or have improved disease resistance,animal welfare and product quality.Recent advances in precise genome editing technologies,especially clustered regularly interspaced short palindromic repeat(CRISPR)/Cas9 nucleases,are enabling the systematic development of gene-edited ruminant production.This review covers the development of gene-edited ruminants,the particulars of site-specific engineered nucleases and the state of the art and new insights into practical applications and social acceptance of genome editing technology in ruminants.It is concluded that the production of gene-edited ruminants is feasible and through improvements in genome editing technology it is possible to help feed the world.展开更多
Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspar...Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspartic acid) grafted with diethylenetriamine, lysine and cholic acid (PEG-PAsp(DETA)-Lys-CA2) polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide (LPS)-activated interleukin-6 (IL-6) and monocytes chemotactic protein 1 (MCP-1) expression as well as blocked nuclear factor-rd3 (NF-rd3) signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 (IL-10) and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.52109010)the Postdoctoral Science Foundation of China(Grant No.2021M701047)the China National Postdoctoral Program for Innovative Talents(Grant No.BX20200113).
文摘Copula functions have been widely used in stochastic simulation and prediction of streamflow.However,existing models are usually limited to single two-dimensional or three-dimensional copulas with the same bivariate block for all months.To address this limitation,this study developed a mixed D-vine copula-based conditional quantile model that can capture temporal correlations.This model can generate streamflow by selecting different historical streamflow variables as the conditions for different months and by exploiting the conditional quantile functions of streamflows in different months with mixed D-vine copulas.The up-to-down sequential method,which couples the maximum weight approach with the Akaike information criteria and the maximum likelihood approach,was used to determine the structures of multivariate Dvine copulas.The developed model was used in a case study to synthesize the monthly streamflow at the Tangnaihai hydrological station,the inflow control station of the Longyangxia Reservoir in the Yellow River Basin.The results showed that the developed model outperformed the commonly used bivariate copula model in terms of the performance in simulating the seasonality and interannual variability of streamflow.This model provides useful information for water-related natural hazard risk assessment and integrated water resources management and utilization.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61571018 and 61531003).
文摘Micrometric-thin cells(MCs)with alkali vapor atoms have been valuable for research and applications of hyperfine Zeeman splitting and atomic magnetometers under strong magnetic fields.We theoretically and experimentally study the saturated absorption spectra using a 100-μm cesium MC,where the pump and probe beams are linearly polarized with mutually perpendicular polarizations,and the magnetic field is along the pump beam.Because of the distinctive thin chamber of the MC,crossover spectral lines in saturated absorption spectra are largely suppressed leading to clear splittings of hyperfine Zeeman transitions in experiments,and the effect of spatial magnetic field gradient is expected to be reduced.A calculation method is proposed to achieve good agreements between theoretical calculations and experimental results.This method successfully explains the suppression of crossover lines in MCs,as well as the effects of magnetic field direction,propagation and polarization directions of the pump/probe beam on saturated absorption spectrum.The saturated absorption spectrum with suppressed crossover lines is used for laser frequency stabilization,which may provide the potential value of MCs for high spatial resolution strong-field magnetometry with high sensitivity.
文摘BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat RA(D2T RA)that was resistant to either a single ABT or a Janus kinase(JAK)inhibitor(Tofacitinib),but improved with a combination of ABT and JAK inhibitor(Baricitinib,BAT).CASE SUMMARY A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab,Etanercept,Adalimumab,and ABT.According to the European League Against Rheumatism definition,the patient was diagnosed with D2T RA.It was then improved with a combination of ABT and a JAK inhibitor BAT.CONCLUSION ABT combined with BAT may be an acceptable strategy for treating D2T RA.
基金Supported by The Natural Science Foundation of China,No.81170450 to Lu MQ and No.81200308 to Lan TThe PhD Start-up Fund of Natural Science Foundation of Guangdong Province,China,No.S2012040008026The New Star of Science and Technology Foundation of Zhu Jiang in Guangzhou City
文摘AIM:To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis.METHODS:Male Sprague-Dawley rats underwent common bile duct ligation(BDL) for 14 d and were treated with Gardenia jasminoides by gavage.The ef-fects of Gardenia jasminoides on liver fibrosis and the detailed molecular mechanisms were also assessed in human hepatic stellate cells(LX-2) in vitro.RESULTS:Treatment with Gardenia jasminoides decreased serum alanine aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,146.6 ± 15 U/L vs 77 ± 6.5 U/L,P = 0.0007) and aspartate aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,188 ± 35.2 U/L vs 128 ± 19 U/L,P = 0.005) as well as hydroxyproline(BDL vs BDL + 100 mg/kg Gardenia jasminoides,438 ± 40.2 μg/g vs 228 ± 10.3 μg/g liver tissue,P = 0.004) after BDL.Furthermore,Gardenia jasminoides significantly reduced liver mRNA and/or protein expression of transforming growth factor β1(TGF-β1),collagen type?Ⅰ?(Col?Ⅰ) and α-smooth muscle actin(α-SMA).Gardenia jasminoides significantly suppressed the upregulation of TGF-β1,Col?Ⅰand α-SMA in LX-2 exposed to recombinant TGF-β1.Moreover,Gardenia jasminoides inhibited TGF-β1-induced Smad2 phosphorylation in LX-2 cells.CONCLUSION:Gardenia jasminoides exerts antifibrotic effects in the liver fibrosis and may represent a novel antifibrotic agent.
基金the National Natural Science Foundation of China(Grant No.62071012)the National Science Fund for Distinguished Young Scholars of China(Grant No.61225003)National Hi-Tech Research and Development Program of China.
文摘Many terrestrial experiments have been designed to detect domain walls composed of axions or axionlike particles(ALPs), which are promising candidates of dark matter. When the domain wall crosses over the Earth, the pseudoscalar field of ALPs could couple to the atomic spins. Such exotic spin-dependent couplings can be searched for by monitoring the transient-in-time change of the atomic spin precession frequency in the presence of a magnetic field. We propose here a single-species cesium atomic comagnetometer, which measures the spin precession frequencies of atoms in different ground-state hyperfine levels, to eliminate the common-mode magnetic-field variations and search for the exotic nonmagnetic couplings solely between protons and ALPs. With the single-species atomic comagnetometer, we experimentally rule out the possibility that the decay constant of the linear pseudoscalar couplings of ALPs to protons is fp■ 3.71 ×107 Ge V. The advanced system has the potential to constrain the constant to be fp■ 10.7 × 109 Ge V, promising to improve astrophysical constraint level by at least one order of magnitude. Our system could provide a sensitive detection method for the global network of optical magnetometers to search for exotic physics.
基金National Natural Science Foundation of China(No.81760855)Liuzhou City Liver Disease Clinical Research Center Project(No.2018AF10503)Guangxi Postgraduate Education Innovation Program(No.YCSY2020106)。
文摘Objective:To investigate the intervention effect and specific mechanism of Jisheng Shenqi Decoction plus Panax notoginseng and Turmeric on carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Methods:SPF SD rats were randomly divided into control group,model group,and Chinese medicine treatment(low,medium and high dose)groups.The model group and Chinese medicine treatment group were given intraperitoneal injection of 40%CCl4 olive oil solution twice a week.A rat model of liver fibrosis was replicated by the method for 8 weeks.After successful modeling,each drug-administered group was gavaged with corresponding drugs,and the control group and model group were gavaged with equal volume of distilled water,once a day,for 4 weeks.After the last intragastric administration,HE staining and Masson staining were used to observe the pathological morphology of liver tissue,and liver function(ALT,AST)was detected;ELISA method was used to determine transforming growth factorβ(TGF-β),angiotensin II(Ang-Ⅱ),chitinase 3-like protein 1(CHI3L1),interleukin-1(IL-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)content;The expression levels of type I,type III collagen(Col-Ⅰ,Col-Ⅲ)and TGF-βmRNA were determined by RT-PCR.Results:①HE and Masson staining showed that a large number of liver cells in the model group were inflamed and necrotic,the collagen fibers in the liver tissue were extensively proliferated,the fibrous septa were interconnected,and the pseudolobules were formed.Compared with the model group,the levels of ALT,AST,TGF-β,Ang-Ⅱ,CHI3L1,IL-1,IL-6 and TNF-αin the traditional Chinese medicine treatment group were decreased,while the levels of Col-Ⅰ,Col-ⅢThe expressions ofⅢand TGF-βmRNA were decreased,and the effect was most obvious in the middle and high dose groups of traditional Chinese medicine(P<0.01).Conclusion:Jisheng Shenqi Decoction combined with Panax notoginseng and Biejia can significantly improve liver fibrosis induced by CCl4 in rats,and its mechanism may be related to the down-regulation of angiotensin-converting enzyme(ACE)-angiotensin II(Ang-II)-angiotensin II receptor 1(AT1R)signaling pathway related gene expression,reducing the level of related cytokines,promoting the degradation of extracellular matrix and so on.
基金supported by the National Natural Science Foundation of China (Nos.62375002,62071012,61571018,61531003,and 91436210)the National Science Fund for Distinguished Young Scholars of China (No.61225003)the National Hi-Tech Research and Development (863) Program。
文摘High-sensitivity radio-frequency optically pumped magnetometers (RF-OPMs), working without cryogenic condition, play a critical role in magnetic field imaging(MFI) at low frequencies(e.g., 100 Hz to 1 MHz). We introduce the principle of operation and recent developments of RF-OPMs and focus on reviewing the MFI applications in magnetic induction tomography, ultralow-field magnetic resonance imaging, and magnetic particle imaging. For the applications of RF-OPMs, ranging from industrial monitoring to medical imaging and security screening, the unshielded and portable RF-OPMs(and RF-OPM array)techniques are still under the further development for detecting and scanning over the target object for accomplishing the final three-dimensional imaging, and thus extremely require the abilities of active compensation of the ambient magnetic field and sensor miniaturization in the future.
基金funded by the National Key Research and Development Program of China(No.2019YFA0801403)the National Natural Science Foundation of China(No.81670256,81970219,82170261,82000250,81741117)+2 种基金Guangdong Basic and Applied Basic Research Foundation(China)(No.2021A1515011005,2021B1212040006)China Postdoctoral Science Foundation(No.2020M672976)the Fundamental Research Funds for the Central University,Sun Yat-sen University,China(No.22qntd4808).
文摘There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).
基金This work was supported by the NSF Grant No.CMMI 09-28282.
文摘A brief overview of vortex-induced vibration(VIV)of circular cylinders is first given as most of VIVstudies have been focused on this particular bluff cross-section.A critical literature review of VIV of bridge decks thathighlights physical mechanisms central to VIV from a renewed perspective is provided.The discussion focuses on VIVofbridge decks from wind-tunnel experiments,full-scale observations,semi-empirical models and computational fluidsdynamics(CFD)perspectives.Finally,a recently developed reduced order model(ROM)based on truncated Volterraseries is introduced to model VIVof long-span bridges.This model captures successfully salient features of VIVat“lockin”and unlike most phenomenological models offers physical significance of the model kernels.
基金supported by the National Natural Science Foundation of China(No.51778495)the National Key Research and Development Program of China(No.2017YFB1201204)。
文摘A framework was proposed to identify a comprehensive set of aerodynamic admittance functions for bridge decks. The contributions of the cross-spectra between longitudinal and vertical wind velocity components and between turbulence components and gust-induced forces were embedded in the identification procedure. To facilitate application of the identified functions in engineering practice, the concept of an equivalent aerodynamic admittance function was introduced and numerically validated. The equivalent aerodynamic admittance functions of a set of streamlined and bluff cross sections were identified experimentally in a wind tunnel. Buffeting analysis of a bridge deck was carried out and the response predicted using the identified aerodynamic admittance functions compared well with the measured response. In addition, a sensitivity analysis was performed to delineate the influence of aerodynamic and structural parameters on the buffeting response, thereby demonstrating the significance of the proposed identification framework.
基金supported by the National Major Project for Production of Transgenic Breeding(2016ZX08007003)。
文摘Transgenic ruminants are a valuable resource for both animal breeding and biomedical research.The development of transgenic breeding is proceeding slowly,because it suffers from low efficiency of gene transfer and possible safety problems from uncontrolled random integration.However,new breeding methods combined with genome editing and somatic cell nuclear transfer or microinjection can offer an economic and efficient way to produce gene-edited ruminants,which can serve as bioreactors or have improved disease resistance,animal welfare and product quality.Recent advances in precise genome editing technologies,especially clustered regularly interspaced short palindromic repeat(CRISPR)/Cas9 nucleases,are enabling the systematic development of gene-edited ruminant production.This review covers the development of gene-edited ruminants,the particulars of site-specific engineered nucleases and the state of the art and new insights into practical applications and social acceptance of genome editing technology in ruminants.It is concluded that the production of gene-edited ruminants is feasible and through improvements in genome editing technology it is possible to help feed the world.
基金financially supported by the National Natural Science Foundation of China (No. U1401242)National Basic Research Program of China (No. 2015CB755500)+1 种基金the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2013S086)the Fundamental Research Funds for the Central Universities (Nos. 17lgjc01 and 17lgpy08)
文摘Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspartic acid) grafted with diethylenetriamine, lysine and cholic acid (PEG-PAsp(DETA)-Lys-CA2) polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide (LPS)-activated interleukin-6 (IL-6) and monocytes chemotactic protein 1 (MCP-1) expression as well as blocked nuclear factor-rd3 (NF-rd3) signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 (IL-10) and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.