The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ...The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ranging from simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even to hepatocellular carcinoma (HCC). A comprehensive understanding of the mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved. An understanding of the mechanism may provide novel strategies in the prevention and treatment to NASH. Abnormal regulation of bile acid homeostasis emerges as an important mechanism to liver injury. The bile acid homeostasis is critically regulated by the farnesoid X receptor (FXR) that is activated by bile acids. FXR has been known to exert tissue-specific effects in regulating bile acid synthesis and transport. Current investigations demonstrate FXR also plays a principle role in regulating lipid metabolism and suppressing inflammation in the liver. Therefore, the future determination of the molecular mechanism by which FXR protects the liver from developing NAFLD may shed light to the prevention and treatment of NAFLD. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively s...The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy(PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids(BAs) are ligands of farnesoid X receptor(FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potentialuse of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.展开更多
The establishment of a possible connection between neutrino emission and gravitational-wave(GW)bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge.In t...The establishment of a possible connection between neutrino emission and gravitational-wave(GW)bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge.In the Daya Bay experiment,using the data collected from December 2011 to August 2017,a search was per-formed for electron-antineutrino signals that coincided with detected GW events,including GW150914,GW151012,GW151226,GW170104,GW170608,GW 170814,and GW 170817.We used three time windows of±10,±500,and±1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates.The detected electron-antineutrino candidates were consistent with the expected background rates for all the three time windows.Assuming monochromatic spectra,we found upper limits(90%confidence level)of the electron-antineutrino fluence of(1.13-2.44)×10^(11)cm^(-2)at 5 MeV to 8.0×10^(7)cm^(-2)at 100 MeV for the three time w indows.Under the assumption of a Fermi-Dirac spectrum,the upper limits were found to be(5.4-7.0)×10^(9)cm^(2)for the three time windows.展开更多
The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation.Farnesoid X receptor(FXR) is critical for bile acid and lipid homeostasis in liver.However,the role o...The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation.Farnesoid X receptor(FXR) is critical for bile acid and lipid homeostasis in liver.However,the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear.Hence,we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control(C57BL/6) mouse livers during development.Liver samples of male C57BL/6 and Fxr-null mice at6 different ages from prenatal to adult were used.The Fxr-null showed an overall effect to diminish the "day-1 surge" of phase-I gene expression,including cytochrome P450 s at neonatal ages.Among the 185 phase-I genes from 12 different families,136 were expressed,and differential expression during development occurred in genes from all 12 phase-I families,including hydrolysis: carboxylesterase(Ces),paraoxonase(Pon),and epoxide hydrolase(Ephx); reduction: aldoketo reductase(Akr),quinone oxidoreductase(Nqo),and dihydropyrimidine dehydrogenase(Dpyd); and oxidation: alcohol dehydrogenase(Adh),aldehyde dehydrogenase(Aldh),flavin monooxygenases(Fmo),molybdenum hydroxylase(Aox and Xdh),cytochrome P450(P450),and cytochrome P450 oxidoreductase(Por).The data also suggested new phase-I genes potentially targeted by FXR.These results revealed an important role of FXR in regulation of ontogeny of phase-I genes.展开更多
The prediction of reactor antineutrino spectra will play a crucial role as reactor experiments enter the precision era.The positron energy spectrum of 3.5 million antineutrino inverse beta decay reactions observed by ...The prediction of reactor antineutrino spectra will play a crucial role as reactor experiments enter the precision era.The positron energy spectrum of 3.5 million antineutrino inverse beta decay reactions observed by the Daya Bay experiment,in combination with the fission rates of fissile isotopes in the reactor,is used to extract the positron energy spectra resulting from the fission of specific isotopes.This information can be used to produce a precise,data-based prediction of the antineutrino energy spectrum in other reactor antineutrino experiments with different fission fractions than Daya Bay.The positron energy spectra are unfolded to obtain the antineutrino energy spectra by removing the contribution from detector response with the Wiener-SVD unfolding method.Consistent results are obtained with other unfolding methods.A technique to construct a data-based prediction of the reactor antineutrino energy spectrum is proposed and investigated.Given the reactor fission fractions,the technique can predict the energy spectrum to a 2%precision.In addition,we illustrate how to perform a rigorous comparison between the unfolded antineutrino spectrum and a theoretical model prediction that avoids the input model bias of the unfolding method.展开更多
Competition among the two-plasmon decay(TPD)of backscattered light of stimulated Raman scattering(SRS),filamentation of the electron-plasma wave(EPW)and forward side SRS is investigated by two-dimensional particlein-c...Competition among the two-plasmon decay(TPD)of backscattered light of stimulated Raman scattering(SRS),filamentation of the electron-plasma wave(EPW)and forward side SRS is investigated by two-dimensional particlein-cell simulations.Our previous work[K.Q.Pan et al.,Nucl.Fusion 58,096035(2018)]showed that in a plasma with the density near 1/10 of the critical density,the backscattered light would excite the TPD,which results in suppression of the backward SRS.However,this work further shows that when the laser intensity is so high(>10^(16)W/cm^(2))that the backward SRS cannot be totally suppressed,filamentation of the EPW and forward side SRS will be excited.Then the TPD of the backscattered light only occurs in the early stage and is suppressed in the latter stage.Electron distribution functions further show that trapped-particle-modulation instability should be responsible for filamentation of the EPW.This research can promote the understanding of hot-electron generation and SRS saturation in inertial confinement fusion experiments.展开更多
Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex,bioactive or cell-laden scaffolds.However,due to the relatively high viscosity...Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex,bioactive or cell-laden scaffolds.However,due to the relatively high viscosity required to maintain shape fidelity during printing,many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers.In this work,we present a novel poly(N-isopropylacrylamide)(PNIPAAm)-based ink and poloxamer support bath system that produces precise,multi-layered structures on the tens of micrometers scale.The support bath maintains the structure of the ink in a hydrated,heated environment ideal for cell culture,while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction.Through the combination of the PNIPAAm-based ink and poloxamer bath,this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200μm.A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated.As a whole,this work demonstrates the ability to produce precise,acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.展开更多
The society structure plays an important role in shaping the attitudes,beliefs and public opinion.For studying the role of the society structure in opinion dynamics,we analyze the Sznajd model on small-world network f...The society structure plays an important role in shaping the attitudes,beliefs and public opinion.For studying the role of the society structure in opinion dynamics,we analyze the Sznajd model on small-world network formed by adding shortcuts in a lattice consisting of N nodes arranged in a ring and on two-dimensional(2-D)regular lattice.Through computer simulation,we find that there exists a pseudo-phase transition from the coexistence state forφ<φ_(c) to the consensus state forφ>φ_(c),whereφ_(c) is some threshold for the shortcut densityφ,which is dependent of the complex network topology and the dimensionality of complex networks.Our observations indicate the dependence of the opinion dynamics on the complex system topology.展开更多
2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) exposure in humans is associated with marked immune suppressions and increased incidence of lymphoblastic diseases.To elucidate mechanisms of impairments in humoral immune r...2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) exposure in humans is associated with marked immune suppressions and increased incidence of lymphoblastic diseases.To elucidate mechanisms of impairments in humoral immune responses,we used a murine model.Following a 20-week administration of low doses of TCDD,we observed severely reduced antibody titers,dramatically decreased number of splenic Th1 and Th2 cells and an increase in CD19^+ B cells.Transcriptional profiling of CD19^+ B cells showed that markers of pre-B cells were significantly elevated,indicating delayed B cell maturation.These changes in B cells were accompanied by decreases of T helper cell numbers and reduced IgM and IgG titers.A transcriptome analysis of splenic B cells followed by Ingenuity Pathway Analysis(IPA) revealed a set of differentially expressed genes known to play roles in tumorigenesis,cell-proliferation and cell-migration.The most up-regulated transcript gene was Eph receptor A2(EphA2),a known oncogene,and the most down-regulated transcript was ZBTB16 that codes for a negative transcriptional regulator important in epigenetic chromatin remodeling.IPA identified cAMP-responsive element modulator(CREM) and cAMP-responsive element binding protein 1(CREBl) as top upstream regulators.Consistently,a MAPPER promoter database analysis showed that all top dysregulated genes had CREM and/or CREBl binding sites in their promoter regions.In summary,our data showed that chronic TCDD exposure in mice caused suppressed humoral immunity accompanied with profound dysregulation of gene expression in splenic B-lymphocytes,likely through cAMP-dependent pathways.This dysregulation resulted in impairments in T-cell and B-cell differentiation and activation of the tumorigenic transcription program.展开更多
The paper presents an explicit matrix algorithm to solve the problem of an elastic wedge with three loaded surfaces.The algorithm makes use of a recently published concept of transformation matrix,by which the origina...The paper presents an explicit matrix algorithm to solve the problem of an elastic wedge with three loaded surfaces.The algorithm makes use of a recently published concept of transformation matrix,by which the original surface loads are converted to equivalent loads in half-space.The three loaded edges are considered simultaneously.The developed algorithm is used to study the effects of two free edges of a steel block and tapered rollers with different contact angles.The two load-free edges can substantially increase deformation if the two edges are close in distance.The results of the tapered roller simulation show that deformation is considerably sensitive to the contact angle of the tapered roller.The largest deformation appears at the big end of the roller.Furthermore,empirical formulae for correction factors for the calculation of block or quarter-space deformation based on half-space solutions are summarized.展开更多
In this paper, we investigate by numerical simulations the Bak-Sneppenmodel (BSM) for biological evolution on scale-free networks (SFNs) with various degree exponents γ. We find that the punctuated equilibrium is rat...In this paper, we investigate by numerical simulations the Bak-Sneppenmodel (BSM) for biological evolution on scale-free networks (SFNs) with various degree exponents γ. We find that the punctuated equilibrium is rather robust with respect to the network topology. Furthermore, we analyze the evolution of the criticalaverage fitness h fi ∗ and the exponent τ of h fi 0 avalanche as a function of α (i.e., the degree exponent γ). Our observations indicate the dependence of evolutionary dynamicsof BSM on the complex biosystem topology.展开更多
This research reports the preparation and characterization of copper nanoparticles modified by didecyl benzene sulfonate (DBS),The Cu nanoparticles' size was determined to be 40nm by transmission electron microsco...This research reports the preparation and characterization of copper nanoparticles modified by didecyl benzene sulfonate (DBS),The Cu nanoparticles' size was determined to be 40nm by transmission electron microscope(TEM).The X-ray photoelectron spectrometry(XPS) results show that there are interactions between the copper nanoparticles and DBS function group.The nonlinear optical properties were studied by the four-wave mixing method.The value of x^(3)/α0 was found to be 6.9×10^-11 esucm.展开更多
Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial applications.Recently,our lab developed the crosslinker poly(glycolic acid)-...Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial applications.Recently,our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol),which crosslinks P(NiPAAm-co-glycidyl methacrylate)via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry.This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels.The physicochemical properties of the hydrogels including the lower critical solution temperature,crosslinking times,swelling,degradation,peptide release and cytocompatibility were evaluated.The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components.Comparable sol fractions were found for all groups,indicating that inclusion of peptides does not impact crosslinking.Moreover,the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage.The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time.This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels.These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.展开更多
Chronic liver diseases have become a major global health prob-lem and its prevalence has been rapidly rising during the last decade.Extensive studies have identified the major causes for the progression of these disea...Chronic liver diseases have become a major global health prob-lem and its prevalence has been rapidly rising during the last decade.Extensive studies have identified the major causes for the progression of these diseases including chronic viral infections,ge-netic mutations,excessive alcohol consumption,metabolic dis-eases,cholestatic liver injury and toxic effects of medications.1e3 Regardless of the aetiology,multiple common mechanisms,espe-cially the gut-liver-axis,are associated with the pathogenesis and fibrotic disease progression of chronic liver injury.However,it re-mains challenging to develop effective therapeutics due to our limited understanding of these mechanisms.In this special issue,we are excited to present seven review articles and one original research paper.With this collection,we have provided the recent advances in understanding the roles of the gut-liver-axis in the development of a variety of liver diseases.展开更多
Many realistic social networks share some universal characteristic properties,such as the small-world effects and the heterogeneous distribution of connectivity degree,which affect the dynamics in society system,espec...Many realistic social networks share some universal characteristic properties,such as the small-world effects and the heterogeneous distribution of connectivity degree,which affect the dynamics in society system,especially the opinion dynamics in society.To see this,we study the opinion dynamics of the Improved Deffuant Model(IDM)in complex networks.When the two opinions differ by less than the confidence parameterǫ(0<ǫ<1),each opinion moves partly in the direction of the other with the convergence parameterµ,which is a function of the opposite’s degree k;otherwise,the two refuse to discuss and no opinion is changed.We analyze the evolution of the steady opinion s∗as a function of the confidence parameterǫ,the relation between the minority steady opinion smin∗and the individual connectivity k,and find some interesting results that show the dependence of the opinion dynamics on the confidence parameter and on the system topology.This study provides a new perspective and tools to understand the effects of complex system topology on opinion dynamics.展开更多
Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and threedimensional particle-in-cell simulations.With the existence of aperiodic structure on the targe...Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and threedimensional particle-in-cell simulations.With the existence of aperiodic structure on the target surface,the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density.The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target.Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron’islands’ formed by the surface plasma waves on the target surfaces.In other words,the radiation with the fundamental frequency is actually’surface emission,on the target rear surface.Besides the intensity of the component with the fundamental frequency,the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target.The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.展开更多
基金supported by the U.S. National Institutes of Health (NIH,Nos.DK081343 and R01GM104037)fund from the University of Kansas Medical Center and Rutgers University,USA
文摘The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ranging from simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even to hepatocellular carcinoma (HCC). A comprehensive understanding of the mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved. An understanding of the mechanism may provide novel strategies in the prevention and treatment to NASH. Abnormal regulation of bile acid homeostasis emerges as an important mechanism to liver injury. The bile acid homeostasis is critically regulated by the farnesoid X receptor (FXR) that is activated by bile acids. FXR has been known to exert tissue-specific effects in regulating bile acid synthesis and transport. Current investigations demonstrate FXR also plays a principle role in regulating lipid metabolism and suppressing inflammation in the liver. Therefore, the future determination of the molecular mechanism by which FXR protects the liver from developing NAFLD may shed light to the prevention and treatment of NAFLD. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
基金supported by the National Institutes of Health Fund (Nos.DK081343,DK090036 and GM104037 to Grace L.Guo)the National Natural Science Foundation of China (No.81302059)+2 种基金the Natural Science Foundation of Heilongjiang Province of China (No.LC2013C35)the Foundation of Educational Committee of Heilongjiang Province of China (No.12541300)supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry and Science Foundation for The Excellent Youth Scholars of the Fourth Hospital of Harbin Medical University in China
文摘The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy(PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids(BAs) are ligands of farnesoid X receptor(FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potentialuse of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.
基金Daya Bay is supported in part by the Ministry of Science and Technology o f China, the U.S. Department o f Energy, the Chinese Academy of Sciences, the CASCenter for Excellence in Particle Physics, the National Natural Science Foundation of China, the Guangdong provincial government, the Shenzhen municipal government,the China General Nuclear Power Group, Key Laboratory of Particle and Radiation Imaging (Tsinghua University), the Ministry of Education, Key Laboratory ofParticle Physics and Particle Irradiation (Shandong University), the Ministry o f Education, Shanghai Laboratory for Particle Physics and Cosmology, the ResearchGrants Council o f the Hong Kong Special Administrative Region of China, the University Development Fund of the University of Hong Kong, the MOE program forResearch of Excellence at National Taiwan University, National Chiao-Tung University, NSC fund support from Taiwan, the U.S. National Science Foundation, the AlfredP. Sloan Foundation, the Ministry o f Education, Youth, and Sports of the Czech Republic, the Charles University GAUK (284317), the Joint Institute o f NuclearResearch in Dubna, Russia, the National Commission of Scientific and Technological Research of Chile, and the Tsinghua University Initiative Scientific Research Program.
文摘The establishment of a possible connection between neutrino emission and gravitational-wave(GW)bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge.In the Daya Bay experiment,using the data collected from December 2011 to August 2017,a search was per-formed for electron-antineutrino signals that coincided with detected GW events,including GW150914,GW151012,GW151226,GW170104,GW170608,GW 170814,and GW 170817.We used three time windows of±10,±500,and±1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates.The detected electron-antineutrino candidates were consistent with the expected background rates for all the three time windows.Assuming monochromatic spectra,we found upper limits(90%confidence level)of the electron-antineutrino fluence of(1.13-2.44)×10^(11)cm^(-2)at 5 MeV to 8.0×10^(7)cm^(-2)at 100 MeV for the three time w indows.Under the assumption of a Fermi-Dirac spectrum,the upper limits were found to be(5.4-7.0)×10^(9)cm^(2)for the three time windows.
基金supported in the part by the U.S. National Institutes of Health National Institute for Environmental Health Sciences [Grant R01ES-019487 to Xiao-bo Zhong]U.S. National Institutes of Health National Institute of General Medical Sciences [Grants R01GM-087376 and R01GM118367 to Xiao-bo Zhong]
文摘The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation.Farnesoid X receptor(FXR) is critical for bile acid and lipid homeostasis in liver.However,the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear.Hence,we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control(C57BL/6) mouse livers during development.Liver samples of male C57BL/6 and Fxr-null mice at6 different ages from prenatal to adult were used.The Fxr-null showed an overall effect to diminish the "day-1 surge" of phase-I gene expression,including cytochrome P450 s at neonatal ages.Among the 185 phase-I genes from 12 different families,136 were expressed,and differential expression during development occurred in genes from all 12 phase-I families,including hydrolysis: carboxylesterase(Ces),paraoxonase(Pon),and epoxide hydrolase(Ephx); reduction: aldoketo reductase(Akr),quinone oxidoreductase(Nqo),and dihydropyrimidine dehydrogenase(Dpyd); and oxidation: alcohol dehydrogenase(Adh),aldehyde dehydrogenase(Aldh),flavin monooxygenases(Fmo),molybdenum hydroxylase(Aox and Xdh),cytochrome P450(P450),and cytochrome P450 oxidoreductase(Por).The data also suggested new phase-I genes potentially targeted by FXR.These results revealed an important role of FXR in regulation of ontogeny of phase-I genes.
基金Supported in part by the Ministry of Science and Technology of Chinathe U.S.Department of Energy,the Chinese Academy of Sciences,the CAS Center for Excellence in Particle Physics,the National Natural Science Foundation of China+3 种基金the Guangdong provincial governmentthe Shenzhen municipal government,the China General Nuclear Power Group,the Research Grants Council of the Hong Kong Special Administrative Region of China,the Ministry of Education in TWthe U.S.National Science Foundation,the Ministry of Education,Youth,and Sports of the Czech Republic,the Charles University Research Centre UNCE,the Joint Institute of Nuclear Research in Dubna,Russiathe National Commission of Scientific and Technological Research of Chile。
文摘The prediction of reactor antineutrino spectra will play a crucial role as reactor experiments enter the precision era.The positron energy spectrum of 3.5 million antineutrino inverse beta decay reactions observed by the Daya Bay experiment,in combination with the fission rates of fissile isotopes in the reactor,is used to extract the positron energy spectra resulting from the fission of specific isotopes.This information can be used to produce a precise,data-based prediction of the antineutrino energy spectrum in other reactor antineutrino experiments with different fission fractions than Daya Bay.The positron energy spectra are unfolded to obtain the antineutrino energy spectra by removing the contribution from detector response with the Wiener-SVD unfolding method.Consistent results are obtained with other unfolding methods.A technique to construct a data-based prediction of the reactor antineutrino energy spectrum is proposed and investigated.Given the reactor fission fractions,the technique can predict the energy spectrum to a 2%precision.In addition,we illustrate how to perform a rigorous comparison between the unfolded antineutrino spectrum and a theoretical model prediction that avoids the input model bias of the unfolding method.
基金supported by the National Natural Science Foundation of China(Nos.12205274,12275251,12035002,11975215)
文摘Competition among the two-plasmon decay(TPD)of backscattered light of stimulated Raman scattering(SRS),filamentation of the electron-plasma wave(EPW)and forward side SRS is investigated by two-dimensional particlein-cell simulations.Our previous work[K.Q.Pan et al.,Nucl.Fusion 58,096035(2018)]showed that in a plasma with the density near 1/10 of the critical density,the backscattered light would excite the TPD,which results in suppression of the backward SRS.However,this work further shows that when the laser intensity is so high(>10^(16)W/cm^(2))that the backward SRS cannot be totally suppressed,filamentation of the EPW and forward side SRS will be excited.Then the TPD of the backscattered light only occurs in the early stage and is suppressed in the latter stage.Electron distribution functions further show that trapped-particle-modulation instability should be responsible for filamentation of the EPW.This research can promote the understanding of hot-electron generation and SRS saturation in inertial confinement fusion experiments.
基金the National Institutes of Health(P41 EB023833)the National Science Foundation Graduate Research Fellowship Program(A.M.N.)for financial supportsupported by a Rubicon postdoctoral fellowship from the Dutch Research Council(NWO,Project No.019.182 EN.004).
文摘Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex,bioactive or cell-laden scaffolds.However,due to the relatively high viscosity required to maintain shape fidelity during printing,many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers.In this work,we present a novel poly(N-isopropylacrylamide)(PNIPAAm)-based ink and poloxamer support bath system that produces precise,multi-layered structures on the tens of micrometers scale.The support bath maintains the structure of the ink in a hydrated,heated environment ideal for cell culture,while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction.Through the combination of the PNIPAAm-based ink and poloxamer bath,this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200μm.A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated.As a whole,this work demonstrates the ability to produce precise,acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.
基金This work was Supported by the NSFC(10635020)the Programme of Introducing Talents of Discipline to Universities under Grant No.B08033+1 种基金the State Key Development Program of Basic Research of China(2008CB317106)the Key Project of Chinese Ministry of Education(306022 and IRT0624).
文摘The society structure plays an important role in shaping the attitudes,beliefs and public opinion.For studying the role of the society structure in opinion dynamics,we analyze the Sznajd model on small-world network formed by adding shortcuts in a lattice consisting of N nodes arranged in a ring and on two-dimensional(2-D)regular lattice.Through computer simulation,we find that there exists a pseudo-phase transition from the coexistence state forφ<φ_(c) to the consensus state forφ>φ_(c),whereφ_(c) is some threshold for the shortcut densityφ,which is dependent of the complex network topology and the dimensionality of complex networks.Our observations indicate the dependence of the opinion dynamics on the complex system topology.
基金supported by the National Natural Science Foundation of China (No. 21277168, 21525730)the Strategic Priority Research Program of the Chinese Academy of Sciences (Nos. XDB14030401, XDB14030402)Chinese Academy of Sciences President's International Fellowship to Irina Krylova (No. 2015VBC063)
文摘2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) exposure in humans is associated with marked immune suppressions and increased incidence of lymphoblastic diseases.To elucidate mechanisms of impairments in humoral immune responses,we used a murine model.Following a 20-week administration of low doses of TCDD,we observed severely reduced antibody titers,dramatically decreased number of splenic Th1 and Th2 cells and an increase in CD19^+ B cells.Transcriptional profiling of CD19^+ B cells showed that markers of pre-B cells were significantly elevated,indicating delayed B cell maturation.These changes in B cells were accompanied by decreases of T helper cell numbers and reduced IgM and IgG titers.A transcriptome analysis of splenic B cells followed by Ingenuity Pathway Analysis(IPA) revealed a set of differentially expressed genes known to play roles in tumorigenesis,cell-proliferation and cell-migration.The most up-regulated transcript gene was Eph receptor A2(EphA2),a known oncogene,and the most down-regulated transcript was ZBTB16 that codes for a negative transcriptional regulator important in epigenetic chromatin remodeling.IPA identified cAMP-responsive element modulator(CREM) and cAMP-responsive element binding protein 1(CREBl) as top upstream regulators.Consistently,a MAPPER promoter database analysis showed that all top dysregulated genes had CREM and/or CREBl binding sites in their promoter regions.In summary,our data showed that chronic TCDD exposure in mice caused suppressed humoral immunity accompanied with profound dysregulation of gene expression in splenic B-lymphocytes,likely through cAMP-dependent pathways.This dysregulation resulted in impairments in T-cell and B-cell differentiation and activation of the tumorigenic transcription program.
基金the Research Grants Council of Hong Kong(Project No.CityU11213914).
文摘The paper presents an explicit matrix algorithm to solve the problem of an elastic wedge with three loaded surfaces.The algorithm makes use of a recently published concept of transformation matrix,by which the original surface loads are converted to equivalent loads in half-space.The three loaded edges are considered simultaneously.The developed algorithm is used to study the effects of two free edges of a steel block and tapered rollers with different contact angles.The two load-free edges can substantially increase deformation if the two edges are close in distance.The results of the tapered roller simulation show that deformation is considerably sensitive to the contact angle of the tapered roller.The largest deformation appears at the big end of the roller.Furthermore,empirical formulae for correction factors for the calculation of block or quarter-space deformation based on half-space solutions are summarized.
基金L.Guo thanks Prof.W.Li for his valuable suggestions and comments.This work was supported by the NSFC(10635020)the programme of Introducing Talents of Discipline to Universities under Grant No.B08033+1 种基金the State Key Development Program of Basic Research of China(2008CB317103)the Key Project of Chinese Ministry of Education(306022 and IRT0624).
文摘In this paper, we investigate by numerical simulations the Bak-Sneppenmodel (BSM) for biological evolution on scale-free networks (SFNs) with various degree exponents γ. We find that the punctuated equilibrium is rather robust with respect to the network topology. Furthermore, we analyze the evolution of the criticalaverage fitness h fi ∗ and the exponent τ of h fi 0 avalanche as a function of α (i.e., the degree exponent γ). Our observations indicate the dependence of evolutionary dynamicsof BSM on the complex biosystem topology.
文摘This research reports the preparation and characterization of copper nanoparticles modified by didecyl benzene sulfonate (DBS),The Cu nanoparticles' size was determined to be 40nm by transmission electron microscope(TEM).The X-ray photoelectron spectrometry(XPS) results show that there are interactions between the copper nanoparticles and DBS function group.The nonlinear optical properties were studied by the four-wave mixing method.The value of x^(3)/α0 was found to be 6.9×10^-11 esucm.
基金supported by the National Institutes of Health(R01 AR068073 and P41 EB023833).
文摘Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial applications.Recently,our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol),which crosslinks P(NiPAAm-co-glycidyl methacrylate)via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry.This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels.The physicochemical properties of the hydrogels including the lower critical solution temperature,crosslinking times,swelling,degradation,peptide release and cytocompatibility were evaluated.The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components.Comparable sol fractions were found for all groups,indicating that inclusion of peptides does not impact crosslinking.Moreover,the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage.The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time.This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels.These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.
基金This study was supported by the USA National Institutes of Health Grant R01 DK104893 and R01DK-057543VA Merit Award I01BX004033 and 1I01BX001390Research Career Scientist Award IK6BX004477.
文摘Chronic liver diseases have become a major global health prob-lem and its prevalence has been rapidly rising during the last decade.Extensive studies have identified the major causes for the progression of these diseases including chronic viral infections,ge-netic mutations,excessive alcohol consumption,metabolic dis-eases,cholestatic liver injury and toxic effects of medications.1e3 Regardless of the aetiology,multiple common mechanisms,espe-cially the gut-liver-axis,are associated with the pathogenesis and fibrotic disease progression of chronic liver injury.However,it re-mains challenging to develop effective therapeutics due to our limited understanding of these mechanisms.In this special issue,we are excited to present seven review articles and one original research paper.With this collection,we have provided the recent advances in understanding the roles of the gut-liver-axis in the development of a variety of liver diseases.
基金This work was supported by the National Natural Science Foundation of China under Grants 70571027,10635020by the Ministry of Education in China under Grant 306022.
文摘Many realistic social networks share some universal characteristic properties,such as the small-world effects and the heterogeneous distribution of connectivity degree,which affect the dynamics in society system,especially the opinion dynamics in society.To see this,we study the opinion dynamics of the Improved Deffuant Model(IDM)in complex networks.When the two opinions differ by less than the confidence parameterǫ(0<ǫ<1),each opinion moves partly in the direction of the other with the convergence parameterµ,which is a function of the opposite’s degree k;otherwise,the two refuse to discuss and no opinion is changed.We analyze the evolution of the steady opinion s∗as a function of the confidence parameterǫ,the relation between the minority steady opinion smin∗and the individual connectivity k,and find some interesting results that show the dependence of the opinion dynamics on the confidence parameter and on the system topology.This study provides a new perspective and tools to understand the effects of complex system topology on opinion dynamics.
基金supported by the Science Challenge Project(No.TZ2016005)China Postdoctoral Science Foundation(No.2017M620430)+1 种基金National Natural Science Foundation of China(Nos.11435011,11575035,11705180,and 11875241)the National Basic Research Program of China(No.2013CB834101)
文摘Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and threedimensional particle-in-cell simulations.With the existence of aperiodic structure on the target surface,the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density.The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target.Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron’islands’ formed by the surface plasma waves on the target surfaces.In other words,the radiation with the fundamental frequency is actually’surface emission,on the target rear surface.Besides the intensity of the component with the fundamental frequency,the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target.The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.