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| 1 | Fatty liver diseases,bile acids,and FXR显示文摘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. | Yan Zhu Hongxia Liu Min Zhang Grace L.Guo | 2016 | Acta Pharmaceutica Sinica B2016，6，5： | 20 |
| 2 | Farnesoid X receptor,the bile acid sensing nuclear receptor,in liver regeneration显示文摘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. | Guodong Li Grace L.Guo | 2015 | Acta Pharmaceutica Sinica B2015，5，2： | 19 |
| 3 | Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver显示文摘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. | Lai Peng Stephanie Piekos Grace L.Guo Xiao-bo Zhong | 2016 | Acta Pharmaceutica Sinica B2016，6，5： | 5 |
| 4 | Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1显示文摘Bile acids(BAs) are amphipathic molecules important for metabolism of cholesterol,absorption of lipids and lipid soluble vitamins,bile flow,and regulation of gut microbiome.There are over 30 different BA species known to exist in humans and mice,which are endogenous modulators of at least 6 different membrane or nuclear receptors.This diversity of ligands and receptors play important roles in health and disease;however,the full functions of each individual BA in vivo remain unclear.We generated a mouse model lacking the initiating enzymes,CYP7 A1 and CYP27 A1,in the two main pathways of BA synthesis.Because females are more susceptible to BA related diseases,such as intrahepatic cholestasis of pregnancy,we expanded this model into female mice.The null mice of Cyp7 a1 and Cyp27 a1 were crossbred to create double knockout(DKO) mice.BA concentrations in female DKO mice had reductions in serum(63%),liver(83%),gallbladder(94%),and small intestine(85%),as compared to WT mice.Despite low BA levels,DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation,synthesis,conjugation,and transport.Additionally,through treatment with a synthetic FXR agonist,GW4064,female DKO mice responded to FXR activation similarly to WT mice. | Daniel Rizzolo Bo Kong Rulaiha E.Taylora Anita Brinker Michael Goedken Brian Buckley Grace L.Guo | 2021 | Acta Pharmaceutica Sinica B2021，11，12： | 4 |
| 5 | 查看详情显示文摘 | H.H.Fan L.Guo K.F.Li M.S.Wong andK.W.Cheah | | 0，，17： | 1 |
| 6 | Chronic TCDD exposure results in the dysregulation of gene expression in splenic B-lymphocytes and in the impairments in T-cell and B-cell differentiation in mouse model显示文摘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. | Yu Feng Jijing Tian Irina Krylova Tuan Xu Heidi Qunhui Xie Tai L.Guo Bin Zhao | 2016 | Journal of Environmental Sciences2016，28，1： | 1 |
| 7 | Development of a converter made of scintillator and wavelength-shifting fibers for fast neutron radiography显示文摘 | Y.Zou L.Guo Z.Guo | | 0，，： | 1 |
| 8 | Adenovirus-mediated intra-arterial delivery of cellular repressor of E1A-stimulated genes inhibits neointima formation in rabbits after balloon injury显示文摘 | Y.Exp Cell ResHan L.Guo C.Yan P | | 0，，： | 1 |
| 9 | CREG inhibits migration of human vascular smooth muscle cells by mediating IGF-Ⅱ endocytosis显示文摘 | Y.Han J.Cui J.Tao L.Guo P | | 0，，： | 1 |
| 10 | CREG promotes a mature smooth muscle cell phenotype and reduces neointimal formation in balloon-injured rat carotid artery显示文摘 | Y.Han J.Deng L.Guo C | | 0，，： | 1 |
| 11 | 查看详情显示文摘 | L.Guo Q.Wang Q.Q.Jiang | | 0，，： | 1 |
| 12 | A dual-gelling poly(N-isopropylacrylamide)-based ink and thermoreversible poloxamer support bath for high-resolution bioprinting显示文摘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. | Adam M.Navara Yu Seon Kim Yilan Xu Christopher L.Crafton Mani Diba Jason L.Guo Antonios G.Mikos | 2022 | Bioactive Materials2022，7，8： | 1 |
| 13 | Search for electron-antineutrinos associated with gravitational-wave events GW150914,GW151012,GW151226,GW170104,GW170608,GW170814,and GW170817 at Daya Bay显示文摘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. | F.P.An A.B.Balantekin H.R.Band M.Bishai S.Blyth G.F.Cao J.Cao J.F.Chang Y.Chang H.S.Chen S.M.Chen Y.Chen Y.X.Chen J.Cheng Z.K.Cheng J.J.Cherwinka M.C.Chu J.P.Cummings O.Dalager F.S.Deng Y.Y.Ding M.V.Diwan T.Dohnal J.Dove M.Dvorak D.A.Dwyer J.P.Gallo M.Gonchar G.H.Gong H.Gong W.Q.Gu J.Y.Guo L.Guo X.H.Guo Y.H.Guo Z.Guo R.W.Hackenburg S.Hans M.He K.M.Heeger Y.K.Heng A.Higuera Y.K.Hor Y.B.Hsiung B.Z.Hu J.R.Hu T.Hu Z.J.Hu H.X.Huang X.T.Huang Y.B.Huang P.Huber D.E.Jaffe K.L.Jen X.L.Ji X.P.Ji R.A.Johnson D.Jones L.Kang S.H.Kettell S.Kohn M.Kramer T.J.Langford J.Lee J.H.C.Lee R.T.Lei R.Leitner J.K.C.Leung F.Li J.J.Li Q.J.Li S.Li S.C.Li W.D.Li X.N.Li X.Q.Li Y.F.Li Z.B.Li H.Liang C.J.Lin G.L.Lin S.Lin J.J.Ling J.M.Link L.Littenberg B.R.Littlejohn J.C.Liu J.L.Liu C.Lu H.Q.Lu J.S.Lu K.B.Luk X.B.Ma X.Y.Ma Y.Q.Ma C.Marshall D.A.Martinez Caicedo K.T.MeDonald R.D.McKeown Y.Meng J.Napolitano D.Naumov E.Naumova J.P.Ochoa-Ricoux A.OIshevskiy H.-R.Pan J.Park S.Patton J.C.Peng C.S.J.Pun F.Z.Qi M.Qi X.Qian N.Raper J.Ren C.Morales Reveco R.Rosero B.Roskovec X.C.Ruan H.Steiner J.L.Sun T.Tmej K.Treskov W.-H.Tse C.E.Tull B.Viren V.Vorobel C.H.Wang J.Wang M.Wang N.Y.Wang R.G.Wang W.Wang W.Wang X.Wang Y.Wang Y.F.Wang Z.Wang Z.Wang Z.M.Wang H.Y.Wei L.H.Wei L.J.Wen K.Whisnant C.G.White H.L.H.Wong E.Worcester D.R.Wu F.L.Wu Q.Wu W.J.Wu D.M.Xia Z.Q.Xie Z.Z.Xing J.L.Xu T.Xu T.Xue C.G.Yang L.Yang Y.Z.Yang H.F.Yao M.Ye M.Yeh B.L.Young H.Z.Yu Z.Y.Yu B.B.Yue S.Zeng Y.Zeng L.Zhan C.Zhang F.Y.Zhang H.H.Zhang J.W.Zhang Q.M.Zhang X.T.Zhang Y.M.Zhang Y.X.Zhang Y.Y.Zhang Z.J.Zhang Z.P.Zhang Z.Y.Zhang J.Zhao L.Zhou H.L.Zhuang J.H.Zou | 2021 | Chinese Physics C2021，45，5： | 1 |
| 14 | An explicit solution to a three-dimensional wedge problem considering two edges effect显示文摘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. | L.GUO Z.M.ZHANG W.WANG Y.ZHAO P.L.WONG | 2020 | Friction2020，8，2： | 0 |
| 15 | Enhancement of the surface emission at the fundamental frequency and the transmitted high-order harmonics by pre-structured targets显示文摘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. | K.Q.Pan D.Yang L.Guo Z.C.Li S.W.Li C.Y.Zheng S.E.Jiang B.H.Zhang X.T.He | 2019 | High Power Laser Science and Engineering2019，7，2： | 0 |
| 16 | Altered gut-liver axis in liver diseases显示文摘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. | Huiping Zhou Jasmohan S.Bajaj Grace L.Guo | 2019 | Liver Research2019，3，1： | 0 |
| 17 | Evaluating the physicochemical effects of conjugating peptides into thermogelling hydrogels for regenerative biomaterials applications显示文摘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. | Hannah A.Pearce Emily Y.Jiang Joseph W.R.Swain Adam M.Navara Jason L.Guo Yu Seon Kim Andrew Woehr Jeffrey D.Hartgerink Antonios G.Mikos | 2021 | Regenerative Biomaterials2021，8，6： | 0 |
| 18 | Farnesoid X receptor and fibroblast growth factor 15/19 as pharmacological targets显示文摘The farnesoid X receptor(FXR)is a nuclear receptor and transcriptional regulator activated by bile acids or synthetic FXR agonists.FXR is expressed highly in the liver and intestine where modulation of FXR critically regulates the expression of genes involved in cholesterol and bile acid homeostasis,hepatic gluconeogenesis/lipogenesis,and inflammation.We review the roles of FXR and one of its intestinal target genes,fibroblast growth factor(FGF)15 in mice/FGF19 in humans,play in regulating these important pathways in health and diseases.The main purpose of this review is to review therapeutics that target bile acid signaling to treat non-alcoholic steatohepatitis(NASH),a stage of disease within the spectrum of non-alcoholic fatty liver disease(NAFLD)with a focus on current preclinical studies in mice and clinical research.NASH is a huge medical burden and characterized by hepatic steatosis,inflam-mation,and progressive development of liver fibrosis.However,there is currently no Food and Drug Administration approved treatment option for NASH.While there are multiple factors contributing to NASH pathophysiology,bile acid regulation is proposed to have a major role in NASH pathogenesis.Synthetic FXR agonists and FGF19 protein may be promising agents to treat NASH,with obeticholic acid(OCA),cilofexor,tropifexor,nidufexor,EDP-305,and NGM282 currently in phase II or III clinical trials of NASH.FXR antagonism has also emerged,and antagonists like ursodeoxycholic acid(UDCA)and glycine-beta-muricholic acid(Gly-MCA)are in pre-clinical stage development for NASH treatment.This mini review seeks to evaluate and organize the literature available on FXR ligands and pathways for the treatment of NASH. | Syeda Maliha Grace L.Guo | 2021 | Liver Research2021，5，3： | 0 |
| 19 | Continuous Opinion Dynamics in Complex Networks显示文摘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. | L.Guo X.Cai | 2009 | Communications in Computational Physics2009，5，5： | 0 |
| 20 | Editorial显示文摘Bile acids have been traditionally viewed as detergent molecules involved in the solubilization and absorption of lipids and lipidsoluble vitamins from the intestines.However,as a result of intensive research over the past two decades,bile acids are now viewed as endocrine signaling molecules that activate specific nuclear receptors and G-protein coupled receptors regulating nutrient metabolism in the liver and intestines.The year | Grace L.Guo Huiping Zhou | 2015 | Acta Pharmaceutica Sinica B2015，5，2： | 0 |
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