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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes 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 Okabe 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 Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes 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 Diabetes and Obesity 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 Biomedical Laboratory 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 insulin.In type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-cells.Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.Consequently,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell function.We and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation capacity.Default transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 methyltransferase.In the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell identity.The transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin modification.Targeting EZH2 is fundamental toβ-cell regenerative potential.Reprogrammed pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex vivo.These pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration Research 2024年第4期19卷 881-886页

作者： Fan Bu jia-Wei Min Md Abdur Razzaque Ahmad el Hamamy Anthony Patrizz Li Qi Akihiko Urayama jun Li Department of Neurology University of Texas Health Science Center Department of Neurology&Psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6j)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite Pak1 Rac1 sensorimotor recovery

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Toward understanding the microstructure characteristics,phase selection and magnetic properties of laser additive manufactured Nd-Fe-B permanent magnets

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International journal of Extreme Manufacturing 2024年第1期6卷 277-294页

作者： Bo Yao Nan Kang Xiangyu Li Dou Li Mohamed el Mansori jing Chen Haiou Yang Hua Tan Xin Lin State Key Laboratory of Solidiffcation Processing Northwestern Polytechnical UniversityXi’anShaanxi 710072People’s Republic of China Arts et Metiers Institute of Technology MSMPHESAM UniversitéF-51006 Chˆalons-en-ChampagneFrance Key Laboratory of Metal High Performance Additive Manufacturing and Innovative Design MIIT ChinaNorthwestern Polytechnical UniversityXi’anShaanxi 710072People’s Republic of China Texas A&M Engineering Experiment Station Institute for Manufacturing SystemsCollege StationTX 77843United States of America

Nd-Fe-B permanent magnets play a crucial role in energy conversion and electronic devices.The essential magnetic properties of Nd-Fe-B magnets,particularly coercivity and remanent magnetization,are significantly infuenced by the phase characteristics and microstructure.In this work,Nd-Fe-B magnets were manufactured using vacuum induction melting(VIM),laser directed energy deposition(LDED)and laser powder bed fusion(LPBF)technologies.Themicrostructure evolution and phase selection of Nd-Fe-B magnets were then clarified in detail.The results indicated that the solidification velocity(V)and cooling rate(R)are key factors in the phase selection.In terms of the VIM-casting Nd-Fe-B magnet,a large volume fraction of theα-Fe soft magnetic phase(39.7 vol.%)and Nd2Fe17Bxmetastable phase(34.7 vol.%)areformed due to the low R(2.3×10-1?C s-1),whereas only a minor fraction of the Nd2Fe14B hard magnetic phase(5.15 vol.%)is presented.For the LDED-processed Nd-Fe-B deposit,although the Nd2Fe14B hard magnetic phase also had a low value(3.4 vol.%)as the values of V(10-2m s-1)and R(1.45×106?C s-1)in the LPBF process resulted in the substantial formation of the Nd2Fe14B hard magnetic phase(55.8 vol.%)directly from the liquid,while theα-Fe soft magnetic phase and Nd2Fe17Bxmetastable phase precipitation are suppressed in the LPBF-processed Nd-Fe-B magnet.Additionally,crystallographic texture analysis reveals that the LPBF-processedNd-Fe-B magnets exhibit isotropic magnetic characteristics.Consequently,the LPBF-processed Nd-Fe-B deposit,exhibiting a coercivity of 656 k A m-1,remanence of 0.79 T and maximum energy product of 71.5 k j m-3,achieved an acceptable magnetic performance,comparable to other additive manufacturing

关键词： laser additive manufacturing(LAM) Nd-Fe-B permanent magnets numerical simulation microstructure magnetic properties

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Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

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Molecular Plant 2024年第5期17卷 747-771页

作者： David R.Nelson Alexandra Mystikou Ashish jaiswal Cecilia Rad-Menendez Michael j.Preston Frederik De Boever Diana C.el Assal Sarah Daakour Michael W.Lomas jean-Claude Twizere David H.Green William C.Ratcliff Kourosh Salehi-Ashtiani Division of Science and Math New York University Abu DhabiAbu DhabiUAE Center for Genomics and Systems Biology(CGSB) New York University Abu DhabiAbu DhabiUAE Biotechnology Research Center Technology Innovation InstitutePO Box 9639Masdar CityAbu DhabiUAE Culture Collection of Algae and Protozoa Scottish Association for Marine ScienceObanScotlandUK National Center for Marine Algae and Microbiota Bigelow Laboratory for Ocean SciencesEast BoothbayMEUSA Laboratory of Viral Interactomes GIGA InstituteUniversity of LiegeLiegeBelgium School of Biological Sciences Georgia Institute of TechnologyAtlantaGAUSA

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

关键词： macroalgae multicellularity comparative genomics evolution adhesome endogenous viral elements

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Therapeutic and regenerative potential of different sources of mesenchymal stem cells for cardiovascular diseases

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BIOCelL 2024年第4期48卷 559-569页

作者： YARA ALZGHOUL HALA j.BANI ISSA AHMAD K.SANAjLEH TAQWA ALABDUH FATIMAH RABABAH MAHA AL-SHDAIFAT EjLAL ABU-el-RUB FATIMAH ALMAHASNEH RAMADA R.KHASAWNEH AYMAN ALZU’BI HUTHAIFA MAGABLEH Department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbidJordan

Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.

关键词： Bone marrow mesenchymal stem cells Adipose tissue mesenchymal stem cells Dental pulp stem cells Umbilical cord mesenchymal stem cells Cardiomyocytes Regeneration Myocardial infarction Mesenchymal stem cells Differentiation Immunomodulation

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Experimental design of paraffin/methylated melamine-formaldehyde microencapsulated composite phase change material and the application in battery thermal management system

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journal of Materials Science & Technology 2024年第2期169卷 124-136页

作者： Que Huang Silong Wang jichun He Dengji Xu Safaa NAbdou Mohamed MIbrahim Shiqi Sun Yanjun Chen Handong Li Ben Bin Xu Changcheng Liu Zeinhom M.el-Bahy Zhanhu Guo School of Environment and Safety Engineering North University of ChinaTaiyuan 030051China Institute of Advanced Energy Materials and Systems North University of ChinaTaiyuan 030051China School of Resources and Safety Engineering Central South UniversityChangsha 410010China School of Medical and BioInformation Engineering Northeastern UniversityShenyang 110819China Department of Chemistry Khurmah University CollegeTaif UniversityP.O.Box 11099Taif 21944Saudi Arabia Department of Chemistry College of ScienceTaif UniversityP.O.Box 11099Taif 21944Saudi Arabia Mechanical and Construction Engineering Faculty of Engineering and EnvironmentNorthumbria UniversityNewcastle Upon Tyne NE18STUK College of Materials Science and Engineering Taiyuan University of Science and TechnologyTaiyuan 030024China Department of Chemistry Faculty of ScienceAl-Azhar UniversityNasr City 11884CairoEgypt

In order to maintain the optimal operating temperature of the battery surface and meet the demand for thermal storage technology,battery thermal management system based on phase change materials has attracted increasing interest.In this work,a kind of core-shell structured microcapsule was synthesized by an in-situ polymerization,where paraffin was used as the core,while methanol was applied to mod-ify the melamine-formaldehyde shell to reduce toxicity and improve thermal stability.Moreover,three different types of heat conductive fillers with the same content of 10 wt.%,i.e.,nano-Al_(2)O_(3),nano-ZnO and carbon nanotubes were added,generating composites.The microcapsules were uniform,and were not affected by the thermal fillers,which were evenly dispersed around.The composite sample with carbon nanotubes(10 wt.%)showed the highest thermal conductivity of 0.50 W/(m K)and latent heat of 139.64 j/g.Furthermore,according to the leakage testing and battery charge/discharge experiments,compared with Al_(2)O_(3)and ZnO,the addition of carbon nanotubes remarkably enhances the heat storage ability as latent heat from 126.98 j/g for the prepared sample with Al_(2)O_(3)and 125.86 j/g for the one with ZnO,then to 139.64 j/g,as well as dissipation performance as a cooling effect by decreasing the sur-face temperature of battery from 2%to 12%of microcapsule,composite sample with carbon nanotubes presents a broad application prospect in battery thermal management system and energy storage field.

关键词： Microcapsule Phase change material Battery Carbon nanotube Safety

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Development and Evaluation of The Implementation of a Preceptorship Program for The Novice ICU Nurse Intensive Care Unit -A Secondary Publication

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journal of Clinical and Nursing Research 2024年第3期8卷 158-175页

作者： Annie Perron Manon Champagne Abir el-Haouly University of Quebec in Abitibi-Témiscamingue Rouyn-NorandaQC J9X 5E4Canada

This study focused on the development and evaluation of the implementation of a preceptorship program adapted to ICU practice in the Ab.-T.region to provide preceptors with tools to support novice nurses.This action research was made possible with the involvement of the centers,preceptors,and novice nurses throughout the development and implementation of the program.This approach enabled participants to take ownership of the training content and fully utilize various tools.The program was implemented throughout the CISSS,where this study was subsequently carried out.Several novices mentioned that the program reinforced their sense of security and made them feel more equipped to handle complex care situations.The preceptors said they were better equipped to offer clinical support and novices were better prepared to work in the ICU.It is important to evaluate the development of the novice nurses’skills following their participation in this program and the long-term impact of this preceptorship.

关键词： Preceptorship program Intensive care unit Novice ICU nurses

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Study of Utilization of Embedded Metal Nanoparticles in Dielectric Thin Film for Humidity Sensing

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Photonic Sensors 2020年第2期10卷 155-161页

作者： Hala j.el-KHOZONDAR Waleed S.MOHAMMED Islamic University of Gaza Electrical Engineering DepartmentGaza-108Palestine Bangkok University BU-CROCCSSchool Of EngineeringPathumthani 12120Thailand

This paper presents a theoretical study of the utilization of the shift in the reflection peak of the thin dielectric film with embedded metal nanoparticles(NPs)towards humidity and vapor applications.The presence of the NPs in the film results in a complex effective index.Hence,the reflected light at the superstrate-film interface causes a phase shift when the index of the surrounding is changed.This alters the reflected spectrum of the formed Fabry-Perot,for both the reflection peak wavelength and intensity.Here,the dynamic range of the proposed sensor is optimized through the variation of the film thickness and nanoparticle metal type,as well as the volume fraction.

关键词： Nanoparticles polymer film humidity sensor

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Ibuprofen-Induced Toxic Epidermal Necrolysis: A Case Report

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International journal of Dermatology And Venereology 2024年第2期7卷 108-110页

作者： Kannappilly Nevin Peediyakkal Mohamed Z. Khatib Mohamad Y. Ananthegowda Dore C. elshafei Moustafa S. Zeer Hani el Shaik Karimulla S. AlFayoumi Moayad M. Mutkule Dyaneshwar P. Soliman Ahmed A. Nashwan Abdulqadir j. Critical Care Department Hamad Medical Corporation (HMC) Doha Qatar.

Introduction: Toxic epidermal necrolysis (TEN) is a medical emergency that most commonly occurs as an adverse effect of certain drugs. Here, we describe a case of a 41-year-old man with no comorbid illness who developed TEN.Case presentation: The patient had been prescribed ibuprofen for myalgia and developed skin lesions after the single dose. The lesions were erythematous papules and macules distributed all over the body after ibuprofen intake. TEN was diagnosed based on the patient’s clinical presentation and laboratory findings. He was treated with intravenous dexamethasone, intravenous immunoglobulin, and cyclosporine. Daily dressing changes and skin care was done with saline, chlorhexidine, and liquid paraffin. The patient was intubated and tracheostomized, and he gradually improved and survived. Later, he developed septicemia in the intensive care unit and was treated successfully.Discussion: The management of TEN includes cessation of the causative cause, multidisciplinary intensive care unit (ICU) care, prevention and early detection of sepsis, fluid and electrolyte balance, adequate analgesia and temperature control, proper organ support, aggressive nutritional management, and good psychological support. The pharmacological therapy for TEN includes corticosteroids, intravenous immunoglobulin, and cyclosporine. The key elements of management are aseptic care and proper dressing of the skin.Conclusion: TEN is associated with high mortality if not managed in a systemic and protocolized way.

关键词： ibuprofen toxic epidermal necrolysis erythema drug-induced erythema

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The impact of maternal immune activation on the morphology and electrophysiological properties of postnatally-born neurons in the offspring

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Neural Regeneration Research 2024年第2期19卷 399-400页

作者： Emilio j.Galván Angelica Zepeda Departamento de Farmacobiología CINVESTAV Unidad Sur CdMxMéxico、Centro de Investigaciones sobre el EnvejecimientoCIE-CinvestavCdMxMéxico Departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoUNAMCdMxMéxico

Pregnancy comes with a combination of physical changes and physiological immunosuppression that increases the susceptibility of women to pathogens and in turn,rises the prevalence of infectious diseases.

关键词： prevalence activation impact

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