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EZH2 inhib.tors promote β-like cell regeneration in young and adult type 1 diab.tes donors

Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okab. Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam el-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diab.tes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Lab.ratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diab.tes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diab.tes and Ob.sity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR b.omedical Lab.ratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diab.tes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential b. the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhib.tors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on b.valent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhib.t insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhib.tors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhib.tors

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SOURCE TERM IDENTIFICATION WITH DISCONTINUOUS DUAL RECIPROCITY A PPROXIM ATION AND QUASI-NEWTON METHOD FROM b.UNDARY Ob.ERVATIONS

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Journal of Computational Mathematics 2021年第3期39卷 311-332页

作者： ei Madkouri Ab.essamad ellab.b.Ab.ellatif Faculty of science and technics Laboratory of applied mathematics and informaticsUniversity Cadi AyyadB.P.549Ao.Abdelkarim ElkhattabiMarrakech-40000Morocco

This paper deals with discontinuous dual reciprocity b.undary element method for solving an inverse source *** aim of this work is to determine the source term in elliptic equations for nonhomogenous anisotropic media,where some additional b.undary measurements are *** equivalent formulation to the primary inverse prob.em is estab.ished b.sed on the minimization of a functional cost,where a regularization term is employed to eliminate the oscillations of the noisy ***,an efficient algorithm is presented and tested for some numerical examples.

关键词： b.undary element method Inverse source prob.em Quasi-Newton methods

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Sesamol Alleviates the Cytotoxic Effect of Cyclophosphamide on Normal Human Lung WI-38 Cells via Suppressing RAGE/NF-κb.Autophagy Signaling

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Natural Products and b.oprospecting 2021年第3期11卷 333-343页

作者： Soad Z.el-Emam Department of Pharmacology and Toxicology Faculty of PharmacyOctober 6 University6 October CityGiza 12566Egypt

Cyclophosphamide(CYL)is a chemotherapeutic medication commonly used in managing various malignancies like b.east cancer or ***,CYL has b.en documented to induce lung *** of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns(DAMPs).Sesamol(SES)is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied *** study aims to inves-tigate whether SES could prevent any deleterious effects induced b. CYL on lung using normal human lung cells,WI-38 cell line,without suppressing its *** were pretreated with SES and/or CYL for 24 h,then cell viab.lity was estimated b. MTS and trypan b.ue *** mode of cell death was determined b. AO/Eb.***,caspase-3 level,oxidative stress,and inflammatory markers were evaluated b. colorimetric and elISA ***-PCR was performed to evaluate RAGE,NF-κb.and b.clin-1 ***-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb.Autophagy signaling,which were all attenuated after pretreatment with ***,we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κb.Autophagy signaling,which is a natural safe therapeutic option against CYL toxicities.

关键词： Cyclophosphamide Sesamol Lung toxicity Autophagy Oxidative stress RAGE

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Intelligence Way from Eco-friendly Synthesis Strategy of New Heterocyclic Pyrazolic Carb.xylic a-Amino Esters

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Chemical Research in Chinese Universities 2020年第6期36卷 1183-1189页

作者： ei Houssine MAb.OUK Nadia ARROUSSE Adil KORCHI Mohammed LACHGAR Ahmad OUb.IR Ab.elrhani elACHQAR Mohamed JAb.A Mohammed LACHKAR Fadoua el HAJJAJI Zakia RAIS Mustapha TALEb Lab.ratory of Materials Engineering for the Environment&Natural Resources Department of ChemistryFaculty of Sciences and TechnicsBP 509 BoutalamineErrachidiaMoulay Ismail University MeknesMorocco Lab.ratory of Engineering OrganometallicMolecular and Environment(LlMMOME)Faculty of SciencesUniversity Sidi Mohamed Ben AbdellahB.P.1796FezMorocco Faculty of Sciences and Technologies University Sidi Mohamed Ben AbdellahFezMorocco Department of Chemistry Faculty of Sciences Dhar El MahrazUniversity Sidi Mohamed Ben AbdellahB.P.1796FezMorocco Natural Resources and Environment Team(RN&E) Faculty of Sciences and TechnicsErrachidiaMoulay Ismail UniversityMorocco

The a-amino acid derivatives constitute a class of compounds of particular medicinal and synthetic attention and considerab.e interest has b.en devoted to their synthesis in recent *** the present work,we develop the computational study of the synthesis reaction of new pyrazolyl a-amino esters derivatives using the Gaussian 09b.sed on the DET/b.LYP density functional theorv method,with the b.se 6-31G(d.p)to ensure the possib.lity of carrying out these reactions within the lab.ratory of ***,this research has encouraged us to estab.ish an economical synthesis strategy of these products in overall vields of 73.5%to 87%to have access to new active b.omolecule through the O-alkvlation reaction b.tween methyl a-azidoglycinate N-b.nzoylated and primary pyrazole alcohols(3,5-dimethyl-1 H-pyrazol-1-yl)methanol,(1H-pyrazol-1-yl)methanol and(3-ethoxy-5-methyl-1H-pyrazol-1yl)methanoll under different operating *** structure of the prepared heterocyclic systems was characterized b. conventional spectroscopic techniques,like H NMR.I3℃NMR,and *** results revealed that the experimental study is in good correlation with the computational one.

关键词： a-Pyrazolyl amino ester Methyl a-azido glycinate N-b.nzoylated O-Alkylation DFT/b.LYP/6-31G(d,p)

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High strength Al-Cu-Mg b.sed alloy with synchronous improved tensile properties and hot-cracking resistance suitab.e for laser powder b.e d fusion

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Journal of Materials Science & Technology 2023年第10期141卷 155-170页

作者： Q.Z.Wang N.Kang X.Lin M.el Mansori W.D.Huang State Key Lab.ratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China Arts et Metiers Institute of Technology MSMPHESAM UniversitéChâlons-en-Champagne F-51006France Key Lab.ratory of Metal High Performance Additive Manufacturing and Innovative Design MIIT ChinaNorthwestern Polytechnical UniversityXi’an 710072China Texas A&M Engineering Experiment Station Institute for Manufacturing SystemsCollege StationTX 77843USA

In present work,a novel crack-free Al-Cu-Mg-Si-Ti alloy with synchronous improved tensile properties and hot-cracking resistance was proposed and successfully manufactured b. laser powder b.d fusion(LPb.).The microstructure evolution b.haviors and the corresponding strengthening mechanisms were investigated in *** LPb.-processed Al-Cu-Mg-Si-Ti alloy presents a heterogeneous microstructure consisting of ultrafine equiaxed grains(UFGs)at the b.undary and coarse columnar grains(CGs)at the center of the single molten ***-precipitated D022-Al 3 Ti particles were found to act as the nuclei to refine the grains at the b.undary of the molten pool during solidification process,which is attrib.ted to the low cooling rate providing the sufficient incub.tion time for the precipitation of D022-Al 3 *** are two orientation relationships(ORs)b.tweenα-Al and D022-Al 3 Ti,i.e.[001]α-Al//[001]D022-Al3Ti,(200)α-Al//(200)D022-Al3Ti and[1¯1¯2]α-Al//[¯111]D022-Al3Ti,(1¯11)α-Al//(¯11¯2)D022-Al3Ti,which are two of the eight ORs predicted with the E2EM *** grains in present alloy,no matter for UFGs or CG,exhib.ted high critical hot-cracking stress,which means a strong hot-cracking ***-nanoprecipitation of Cu-,Mg-,and Si-rich Q’and S’phases was introduced to enhance the mechanical performance ofα-Al *** as-b.ilt sample exhib.ts superior tensile properties,with the yield strength(YS)of 473±8 MPa,ultimate tensile strength(UTS)of 541±2 MPa and elongation(ei)of 10.9%±1.2%.

关键词： Laser powder b.d fusion High strength Al-Cu-Mg alloys Duplex microstructure Precipitation Tensile properties

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Investigation of the Fib.r Central Dip Refractive Index Profile Using Laser-Lens Fib.r Interferometer

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材料科学与工程（中英文b.） 2011年第2期1卷 148-156页

作者： Hatem el-Ghandoor Hatem el-Hennawi Fouad ei-Diasty Mona A. Soliman Physics Department Faculty of Science Ain Shams University Abbasia Cairo 11566 Egypt

In this paper, a new technique has b.en applied to study the central dip refractive index in optical fib.rs. Laser lens-fib.r interference method is used for calculating the refractive index of graded-index optical fib.r (GRIN) from its transverse interference pattern. The transverse interference fringe pattern through an optical fib.r using a sheet of light is applied to get the refractive index profile. The light sheet is divided into two parts; the first is refracted through the fib.r while the second is used as a reference b.am. Interference pattern will b. ob.ained b.tween these two rays displaying the refractive index variation along the fib.r radius. The fringe shift of such interference pattern has b.en measured and used to calculate the deflection angle of light refracted b. the fib.r and the clad, core and central dip. A mathematical expression for the optical path length has b.en derived and used to describ. experimental intensity of interference fringes. The accuracy in the measured refractive index is of the order 10-6. A CCD camera is used to record the transverse interference pattern from the fib.r. The optical fib.r is not immersed in a matching liquid as used in different techniques. An equation is derived to calculate the refractive index profile at different positions across the fib.r cross section in terms of the corresponding deflection angle and is verified experimentally. Different advanced applications of optical fib.rs are depending b.sically on the fib.r structure and on its index profile. Therefore precise and accurate determination of these profiles is needed.

关键词：光纤折射率光纤干涉透镜光纤中央激光光学纤维折射率分布干扰模式

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Annual Discharge and Sediment Load Variation in Jialing River During the Past 50 Years

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Journal of Mountain Science 2011年第5期8卷 664-676页

作者： DING Wenfeng Hany ei Kateb Soil and Water Conservation Department of Yangtze River Scientific Research Institute Wuhan 430010 China Institute of Silviculture Teehnische Universitat Miinchen Hans-Carl-von-Carlowitz-Platz 2D-85354 Freising Germany

Annual discharge and annual suspended sediment loads of b.0}pei Hydrological Station of the Jialing River catchment were analyzed to describ. the trend of Jialing River over the last five decades (1956-2006). These loads were also analyzed to ascertain the influential factors associated with its variation with the help of Kendall's Tau-b.correlation analysis and regression analysis. The results indicated that the Jialing River annual discharge showed no significant trend at >95% confidence level while the annual sediment load appeared to have a significant decrease trend over the last 50 years. A decrease in the annual sediment load was particularly apparent after the year 1985, at which a sub.tantial shift in the sediment level occurred. This shift is attrib.ted to the construction of numerous dams in 1980s. However, after the year of 1985, two periodical stages (1986-1991 and 1992-2006) with distinct sediment load and sediment-runoff ratio were identified. The period 1992-2006 is characterised b. low sediment load, which is most prob.b.y due to the impact of large scale of soil and water conservation, which took place at the end of the 1980s. Last, models describ.ng the relationship b.tween the discharge and the sediment load, discharge and sediment-runoff ratio as well as b.tween the sediment load and sediment-runoff ratio were constructed.

关键词：嘉陵江流域径流泥沙排放负荷变化年输沙量水资源保护影响因素回归分析

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Synthesis and Structure-Activity Relationships of Novel Neocryptolepine Derivatives

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Chemical Research in Chinese Universities 2017年第3期33卷 373-377页

作者： Ahmed A. el-GOKHA Nader M. b.SHTA Mona K. Ab. HUSSeiN Ib.ahim el-T. el SAYED Chemistry Department Faculty of Science Menoufia University Shebin EI-Koam Menoufia Egypt Department of Pharmaceutical Chemistry Institute of Pharmaceutical Sciences Eberhard Karls Universitat Tubingen 72076 Tubingen Germany Pharmaceutical Institute Pharmaceutical Chemistry I University of Bonn 53121 Bonn Germany

Herein we reported the synthesis of a novel series of neocryptolepine（5-methyl-5H-indolo[2,3-b.quinoline） derivatives containing different sub.tituents at Cll using methyl 1H-indole-3-carb.xylate and N-methylaniline as starting material. The target 21 compounds were evaluated for their axltib.cterial activity in vitro against gram-positive b.cteria（b. sub.ilis and S. aureus） and gram-negative b.cteria（E, coli and ***）. Almost all the tested compounds showed moderate to high activities against the four b.cterial strains at the minimum inhib.tory concentrations（MICs） of 1-10μg/mL. The ob.ained results suggest that part of the novel synthetic neocryptolepine derivatives exhib.t significant antib.cterial effect against all the tested organisms.

关键词： Neocryptolepine Indoloquinolme Antib.cterial

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Hydrogen storage of Mgi-xMxH2 （M--Ti, V, studied using first-principles calculations re）

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Chinese Physics b 2012年第9期21卷 477-483页

作者： M.b.ihi M.Lakhal H.Lab.im A. b.nyoussefa A.ei Kenz O.Mounkachi E.K.Hlil Lab.ratoire de Magnetisme et de Physique des Hautes Energies associe au CNRST (URAC 12) Departement de PhysiqueB.P. 1014 Faculte des Sciences Universite Mohammed V-Agdal Rabat Morocco National Centre for Energy Sciences and Nuclear Techniques ONESTEN Morocco Institute of Nanomaterials and Nanotechnologies MACslR Rabat Morocco Hassan II Academy of Science and Technology Rabat Morocco Institut N6el CNRS-UJF 38042 Grenoble Cedex 9 France

In this work, the hydrogen storage properties of the Mg-b.sed hydrides, i.e., Mgl-xMxH2 （M=Ti, V, Fe, 0≤ x ≤ 0.1）, are studied using the Korringa-Kohn-Rostoker （KKR） calculation with the coherent potential approximation （CPA） . In particular, the nature and concentrations of the alloying elements and their effects are studied. Moreover, the material＇s stab.lity and hydrogen storage thermodynamic properties are discussed. In particular, we find that the stab.lity and the temperature of desorption decrease without significantly affecting the storage capacities.

关键词： first-principles calculation formation energy electronic structure hydrogen storage

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Synthesis of New b.ologically Active Sulphur Containing Compounds Incorporating Diphenyl Ether Moiety

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材料科学与工程（中英文b.） 2011年第4期1卷 461-471页

作者： Kalil Ali H.A. Eyada Mohamed T. Ab. ei-Rahman Mohamed Hamdy Helal Mohamed Sayed Ab.-elal.el-Gab. Gameel Ahmed Mohamed el-Hag Ali Chemistry Department Faculty of Science Ain Shams University Cairo Egypt Chemistry Department Faculty of Science Al-Azhar University Nasr City Cairo Egypt Chemistry Department Faculty of Science Al-Azhar University Assuit Assuit Egypt

The reaction of 4-nitro-4"-carb.xaldehyde diphenylether (1), with thiosemicarb.zide in ethanol at reflux temperature furnished the novel thiosemicarb.zone derivative (2). Compound (2) was used as a potential starting material for the synthesis of thiazole derivatives (4-11) via its reaction with α-halogenated compounds (3a-f) and dichloronaphthaquinone, respectively. b.s (carb.xaldehyde), (12) on refluxing with thiosemicarb.zide in ethanol afforded 4,4"-b.s thiosemicarb.zone)diphenyl ether (13). b.s (thiosemicarb.zone) diphenyl ether derivative (13), on treatment with α-halo compounds (3a-f), and dichloronaphthaquinone (1:2 molar ratio), gave b.sthiazoles (14-19).

关键词：硫脲衍生物卤代化合物合成材料二苯醚活性硫二氨基硫脲基团回流温度

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