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Discovering small molecules as Wnt inhibitors that promote heart regeneration and injury repair

Journal of Molecular Cell Biology 2020年第1期12卷 42-54页

作者： Shuying Xie Wenbin Fu Guangju Yu Xueli Hu Kaa Seng Lai Xiangwen Peng Yating Zhou Xuejiao Zhu Ptamen Christov Leah Sawyer terri t.ni Gary A.Sulikowski Zhongzhou Yang Ethan Lee Chunyu Zeng Wei E.Wang tao P.Zhong State Key Laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Department of Cardiology Daping HospitalThird Military Medical UniversityChongqing 400042China Shanghai Key Laboratory of Regulatory Biology Institute of Molecular MedicineEast China Normal University School of Life SciencesShanghai 200241China Vanderbilt Institute of Chemical Biology Vanderbilt UniversityNashvilleTN 37232USA Department of Cell and Developmental Biology Vanderbilt UniversityNashvilleTN 37232USA MOE Key Laboratory of Model Animal for Disease Study Model Animal Research CenterNanjing UniversityNanjingChina

there are intense interests in discovering pro regenerative medicine leads that can promote cardiac differentiation and regeneration,as well as repair damaged heart *** have combined zebrafish embryo-based screens with cardiomyogenesis assays to discover selective small molecules that modulate heart development and regeneration with minimal adverse *** related compounds with novel structures,named as Cardiomogen 1 and 2(CDMG1 and CDMG2),were identified for their capacity to promote myocardial hyperplasia through expansion of the cardiac progenitor cell *** find that Cardiomogen acts as a Wnt inhibitor by targeting p-cat.nin and reducing tcf/Lef-mediated transcription in cultured *** treatment of amputated zebrafish hearts reduces nuclear p-cat.nin in injured heart tissue,increases cardiomyocyte(CM)proliferation,and expedites wound healing,thus accelerating cardiac muscle ***,Cardiomogen can alleviate the functional deterioration of mammalian hearts after myocardial *** hearts exposed to CDMG1 display increased newly formed CMs and reduced fibrotic scar tissue,which are in part attributable to the^-cat.nin *** findings indicate Cardiomogen as a Wnt inhibitor in enhancing injury-induced CM proliferation and heart regeneration,highlighting the values of embryo-based small molecule screens in discovery of effective and safe medicine leads.

关键词： small molecule screen Wnt inhibitor regeneration

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Spin-glass behavior in the competing CoCrGaO_(4)cubic spinel system

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Nano Research 2025年第1期18卷 501-507页

作者： Jiyu Hu Jiangli ni Zhenfa Zi Chaocheng Liu School of Physics and Materials Engineering Hefei Normal UniversityHefei 230009China National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230026China

Spin glasses(SGs),generally defined as disordered systems with randomized competing interactions,are widely investigated complex *** the ground states of spin glasses is crucial for understanding the nature of disordered magnets and many other physical manifestations,while also helping to solve some hard combinatorial optimization problems across multiple ***,the intrinsic cause of SG has always been elusive,especially in spinel oxide ***,we report the SG behavior observed in the cubic spinel oxides CoCrGaO_(4),and provide a comprehensive understanding of its intrinsic *** results indicate a frustrated state under multi-magnetic competition,and the features of SG are confirmed by susceptibility *** fitting parameters ofτ0,t0,and zv of isothermal remanent magnetization further reveal the relaxation behavior and strong spin ***,the varying exchange coupling under different temperatures and magnetic fields is unveiled,which should be responsible for the disordered *** studies unravel the underlying mechanism responsible for doping-induced magnetic frustration and introduce CoCrGaO_(4)as a potential platform for investigating spin glass behavior,thereby advancing fundamental research on frustrated magnetism within the spinel system.

关键词： spin glass(SG) magnetic frustration magnetic competition spinel ferrites

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Pharmacological evaluation of NSAID-induced gastropathy as a “translatable” model of referred visceral sensitivity

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World Journal of Gastroenterology 2017年第33期23卷 6065-6076页

作者： Michele Hummel terri Knappenberger Meghan Reilly Garth t Whiteside Purdue Pharma L.P. Discovery Research

AIM to evaluate whether non-steroidal anti-inflammatory drugs(NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral *** Gastric ulcer pain was induced by the oral administration of indomethacin to male,CD1 mice(n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. these mechanisms included: transient receptor potential(tRP),sodium and acid-sensing ion channels(ASICs) as well as opioid receptors and guanylate cyclase C(GC-C). RESULtS Results showed that two opioids and a GC-C agonist,morphine,asimadoline and linaclotide,respectively,the tRP antagonists,AMG9810 and HC-030031 and the sodium channel blocker,carbamazepine,elicited a dose-and/or time-dependent attenuation of referred visceral hypersensitivity,while the ASIC blocker,amiloride,was ineffective at all doses tested. CONCLUSION together,these findings implicate opioid receptors,GC-C,and sodium and tRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly,these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

关键词： Visceral hypersensitivity Pain translation Guanylate cyclase C Non-steroidal anti-inflammatory drugs transient receptor potential channel

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Hemoglobin integrated red blood cell membrane-coated metalorganic framework nano-platform for improving the self-adaptive blood glucose management

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Nano Research 2025年第1期18卷 618-627页

作者： Shuai Wu Li Zhu Sheng ni Xiong Zhao Meng Yan Yuan Zhong Karissa Kusuma Yi Liang Kaiwen Bao Kai Qu Xian Qin Kun Zhang Wuquan Deng Da Sun Wei Wu Key Laboratory of Biorheological Science and technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China Chongqing University three Gorges Hospital Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic DiseasesChongqing 404000China Institute of Life Sciences&Biomedical Collaborative Innovation Center of Zhejiang Province Wenzhou UniversityWenzhou 325035China Department of Endocrinology School of MedicineChongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400014China

Diabetes,a prevalent chronic metabolic disorder,often leads to severe ***,existing treatment methods may pose life-threat.ning risks due to poor patient compliance and inaccurate dosing of subcutaneous insulin ***,a biomimetic red blood cell(RBC)membrane-coated glucose-responsive nanoplatform is developed for controlling insulin *** nanoplatforms with RBC membrane can prolong the half-life of nano-formulation in vivo mediated by the biomimetic immune ***,the cascade catalytic effect of glucose oxidase(GOx)encapsulated in metal-organic frameworks(MOFs)and hemoglobin(Hb)in the RBC membrane are able to not only facilitate glucose-responsive insulin release,but also eliminate the detrimental by-product hydrogen peroxide(H_(2)O_(2))resulting from the Hb mediated H_(2)O_(2)*** in vitro and in vivo studies have demonstrated the favorable glucose-responsive performances of this advanced nano-platform with a single intravenous injection maintaining blood glucose balance in type 1 Diabetes(t1D)mice for an extended duration without the hypoglycemia ***,this biomimetic insulin delivery system is poised to function as a strategy for the intravenous insulin administration,offering a promising drug candidate for the self-adaptive long-term t1D treatment.

关键词： glucose-responsive metal-organic frameworks red blood cell membrane insulin delivery glucose oxidase hemoglobin

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Scavenging of reactive oxygen and nitrogen species with nanomaterials

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Nano Research 2018年第10期11卷 4955-4984页

作者： Carolina A. Ferreira Dalong ni Zachary t. Rosenkrans Weibo Cai Department of Radiology University of Wisconsin-Madison Madison W153705 USA

Reactive oxygen and nitrogen species （RONS） are essential for normal physiological processes and play important roles in cell signaling, immunity, and tissue homeostasis. However, excess radical species are implicated in the development and augmented pathogenesis of various diseases. Several antioxidants may restore the chemical balance, but their use is limited by disappointing results of clinical trials. Nanoparticles are an attractive therapeutic alternative because they can change the biodistribution profile of antioxidants, and possess intrinsic ability to scavenge RONS. Herein, we review the types of RONS, how they are implicated in several diseases, and the types of nanoparticles with inherent antioxidant capability, their mechanisms of action, and their biological applications.

关键词： mnanomaterials reactive oxygen species(ROS) reactive nitrogen species ROS scavenging antioxidant nanoparticles

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Rapid earthquake focal mechanism inversion using high-rate GPS velometers in sparse network

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Science China Earth Sciences 2015年第11期58卷 1970-1981,1页

作者： GUO AiZhi ni SiDao CHEN WeiWen Jeffrey t.FREYMUELLER SHEN ZhiChao State Key Laboratory of Geodesy and Earth's Dynamics Institute of Geodesy and Geophysics Chinese Academy of Sciences School of Earth and Space Sciences University of Science and Technology of China Geophysical Institute University of Alaska Fairbanks

In this study, we demonstrate an approach for inverting earthquake source parameters based on high-rate global positioning system （GPS） velocity seismograms. the velocity records obtained from single-station GPS velocity solutions with broadcast ephemeris are used directly for earthquake source parameter inversion using the Cut and Paste method, without requiring conversion of the velocity records into displacement records. taking the E1 Mayor-Cucapah earthquake as an example, GPS velocity records from 10 stations with reasonable azimuthal coverage provide earthquake source parameters very close to those from the Global centroid moment tensor （Global CMt） solution. In sparse network tests, robust source parameters with acceptable bias can be achieved with as few as three stations. When the number of stations is reduced to two, the bias in rake angle becomes appreciable, but the magnitude and strike estimations are still robust. the results of this study demonstrate that rapid and reliable estimation of earthquake source parameters can be obtained from GPS velocity data. these parameters could be used for early earthquake warning and shake map construction, because such GPS velocity records can be obtained in real time.

关键词： high-rate GPS velometer GPS velocity determination CAP method earthquake source parameters sparse network

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A Characterization of t_(2g+1,2) among Alternating Knots

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Acta Mathematica Sinica,English Series 2021年第12期37卷 1841-1846页

作者： Yi ni Department of Mathematics CaltechMC 253-371200 E California BlvdPasadenaCA 91125USA

Let K be a genus g alternating knot with Alexander polynomial Δ_(K)(t)=Σ_(i=-g)^(g)a_(i)t^(i).We show that if |a_(g)|=|a_(g-1)|,then K is the torus knot t_(2g+1,±2).this is a special case of the Fox trapezoidal ***... 详细信息

关键词： Alternating knots Alexander polynomial strongly quasipositive fibered knots

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Experimental isothermal section phase diagram of Ho-Fe-In at 773 K and magnetic properties of Ho_(12)Fe_(2.08)In_(2.92) alloy

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Rare Metals 2021年第4期40卷 987-994页

作者： Xiang Chen Chao ni the College of Physics and Electronic Information Engineering Neijiang Normal UniversityNeijiang 641002China the Ames Laboratory U.S.Department of EnergyIowa State UniversityAmesIA 50011-3020USA

the isothermal section of the Ho-Fe-In system at 773 K has been constructed by X-ray powder *** known structure ternary compound Er_(12)Fe_(2) In_(3)-type Ho_(12)Fe_(2) In_(3) has been *** the same time,solid solutions are not detected in Ho-Fe-In system at 773 *** magnetic transition and magnetocaloric effect of Ho_(12)Fe_(2.08)In_(2.92) alloy with Er_(12)Fe_(2) In_(3)-type structure were investigated by magnetic susceptibility and isothermal magnetization *** normal antiferromagnetic-paramagnetic transition and another abnormal one are discovered at 18 and 76 K in ground state,*** to a first-order field-induced metamagnetic transition(antiferromagnetic-ferromagnetic) at/below the Neel temperature of 18 K),the negative entropy changes are observed at corresponding *** is only a second-order ferromagnetic-paramagnetic transition near Curie temperature(tC),the maximum entropy change(Δ_(Smax)) values are-6.14 J·kg^(-1)·K^(-1) at 3 K and 7.88 J·kg^(-1)·K^(-1) at 28 K in a field range of 0-7 *** reversible relative cooling power corresponding to negative entropy change can reach about 600 J·kg^(-1) in an wide operating temperature region Δ_(tcycl)=74 K from 16 to90 K,which suggests that Ho_(12)Fe_(2.08)In_(2.92) could be a potential material for magnetic refrigeration in the corresponding temperature range.

关键词： Re_(3(x+y))(t2)_(x)X_(y)phase Metamagnetic transition Magnetothermal properties Ho-Fe-In alloy

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Dehydration at subduction zones and the geochemistry of slab fluids

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Science China Earth Sciences 2020年第12期63卷 1925-1937页

作者： Wancai Li Huaiwei ni CAS Key Laboratory of Crust-Mantle Materials and Environments School of Earth and Space SciencesUniversity of Science and Technology of ChinaHefei230026China CAS Center for Excellence in Comparative Planetology Hefei230026China

Subducting oceanic slabs undergo metamorphic dehydration with the increase of temperature and pressure during *** is an essential step for element recycling,and slab fluids are critical agents for mediating slab-mantle *** is mainly controlled by the thermal structure of subduction zones and the stability of hydrous *** fore-arc depths,slab dehydration produces aqueous fluid with dissolved salts such as *** subduction proceeds deeper,the content of silicate components *** sub-arc and post-arc depths,a hydrous silicate melt is likely to form,or a supercritical fluid could arise from complete miscibility between silicates and H_(2)*** partitioning of elements between slab fluid and the residual solid rock is controlled by the type of fluid,and generally it is the supercritical fluid that is the most capable of mobilizing trace elements,being an effective carrier even for high field strength *** the chemistry of slab fluids relies on sophisticated integration of experiments,theoretical computation and investigation of natural rock *** contribution focuses on the content and speciation of key volatiles,including carbon,nitrogen and sulfur,in slab fluids as well as important fluid properties such as oxygen fugacity and *** properties of slab fluids show complicated variation under the control of mineral assemblages and t-P *** fluids at great depths of subductions have been inferred to be modestly alkaline and not necessarily very oxidizing as often *** progress in the research of slab dehydration and the chemistry and properties of slab fluids demands urgently the development of innovative experimental and computational technology including in situ analytical methods at high t-P.

关键词： Subduction zone Dehydration Slab fluids Volatiles Oxygen fugacity Acidity

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Ultraviolet humic-like component contributes to riverine dissolved organic matter biodegradation

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Journal of Environmental Sciences 2023年第2期124卷 165-175页

作者： Maofei ni Siyue Li College of Eco-Environmental Engineering Guizhou Minzu UniversityGuiyang 550025China Research Center for Environmental Ecology and Engineering School of Environmental Ecology and Biological EngineeringWuhan Institute of TechnologyWuhan 430205China the karst environmental geological hazard prevention laboratory of Guizhou Minzu University Guiyang 550025China Key Laboratory of Reservoir Aquatic Environment Research Center for EcohydrologyChongqing Institute of Green and Intelligent TechnologyChinese Academy of SciencesChongqing 400714China

Biological degradation of dissolved organic matter(DOM)regulates its structure and fate in river *** views suggested that labile components were dominantly consumed by microbial *** we provide new observations that a part of recalcitrant compounds largely contribute to riverine DOM *** excitationemission matrix fluorescent spectroscopy combined with peak picking and parallel factor analysis are used to explore component variability during DOM ***-like and tryptophan-like DOM are the primary components of riverine DOM,with proportion contributions of 39%–82% and 16%–61% for % of the maximumfluorescence intensity,*** 56 days of aerobic incubation in the dark,large amounts of tyrosine-like DOM generation are *** temperature enhances the decomposition of ultraviolet humiclike substance and further stimulates labile DOM bio-mineralization into carbon ***,averaged proportions of amino acid compositions(peak B and t)markedly increase(pthe humic-like compositions(peak A,M and C)decrease after DOM incubation,suggesting incomplete degradation of refractory DOM from high-molecular to low-molecular weight *** findings support the new notion of the continuous DOM biodegradation in a mode as“steps by steps”,contributing to a new understanding of carbon cycling for the UN Sustainable Development Goal.

关键词： Dissolved organic matter(DOM) Sequential biodegradation Recalcitrant compounds Component and fate Fluorescence analysis

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