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ca^(2+) binding to the c_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

Protein & cell 2024年第4期15卷 305-312页

作者： Han chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.chepurwar Regina célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch carolin Wichmann Nicola Strenzke Barbara Vona julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany collaborative Research center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIc Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging cluster of Excellence(MBExc) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHcs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-c_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHcs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice

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Journal of Integrative Medicine 2024年第5期22卷 600-613页

作者： Mijung Yeom Sora Ahn Dae-Hyun Hahm Sun-young Jang Se Hoon Jang Su-Yang Park Jae-Hwan Jang Jihan Park Ju-young Oh In-Seon Lee Kyuseok Kim Soon-Kyeong Kwon Hi-Joon Park Acupuncture and Meridian Science Research center College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Department of Physiology School of MedicineKyung Hee UniversitySeoul 02447Republic of Korea BioNanocomposite Research center Kyung Hee UniversitySeoul 02447Republic of Korea Department of Science in Korean Medicine College of Korean MedicineGraduate SchoolKyung Hee UniversitySeoul 02447Republic of Korea college of Korean Medicine Kyung Hee UniversitySeoul 02447Republic of Korea Department of Ophthalmology Otorhinolaryngology and Dermatology of Korean MedicineCollege of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Division of Applied Life Science(BK21) Gyeongsang National UniversityJinju 52828Republic of Korea Department of Anatomy&Information Sciences College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea

Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut *** has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely *** purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut *** AD-like skin lesions were induced by applying Mc903 topically to the cheek of the *** was done at the Gok-Ji(LI11)***-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and *** microbiota was profiled using 16S rRNA gene sequencing from fecal *** Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of *** beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated ***,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the *** attenuated these abnormalities,which was gut *** Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for

关键词： Atopic dermatitis Acupuncture Gut microbiota Intestinal barrier function

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Barosinusitis due to routine weather changes:A cross-sectional analysis of public websites

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 18-23页

作者： James c.campbell julia E.canick Philip G.chen Ralph Abi Hachem David W.Jang Department of Head and Neck Surgery&communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Duke University School of Medicine DurhamNorth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery University of Texas Health Science Center San AntonioSan AntonioTexasUSA

Background:Sinusitis is a common diagnosis that can be erroneously associated with routine weather‐related barometric pressure *** actuality,these pressure changes likely exacerbate migraine headaches,which can cause facial pain and pressure rather than true sinus ***:The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the ***:An Internet search for relevant terms was conducted,and content of the resulting pages was assessed for associations between weather‐related pressure changes and either sinusitis or *** in reported results across different subtypes of Internet sources were *** primary outcomes measured were(1)whether a given media source associated barometric weather changes with sinusitis,(2)whether that source associated barometric weather changes with migraine,and(3)treatment options offered by that ***:Of the 116 included webpages,36(31.03%)associated sinusitis and routine barometric pressure *** these,10(27.77%)were otolaryngology practice ***‐seven webpages(57.76%)associated migraine and routine barometric pressure *** these,nonotolaryngology webpages were more likely to report this ***:Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with *** sources were more likely to link weather‐related pressure changes to *** results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

关键词： acute rhinosinusitis balloon sinus dilation headache migraine sinusitis

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Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia G Medina Rita A Gomez julia R Herrera Nancy L Martínez Brenda Hernández Yesenia García Department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico Research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico Epidemiology Research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico Department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BAcKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,c-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-GAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.Pconsidered statistically *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).cONcLUSION Anti-GAD65 positivity was high in our ***-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements

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Deciphering metastatic route-specific signals and their microenvironment interactions in peritoneal metastasis of gastric cancer

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cancer communications 2024年第4期44卷 514-517页

作者： Ki Tae Kim Jae Eun Lee Jae-Ho cheong In cho Yoon young choi Department of Molecular Genetics&Dental Pharmacology School of DentistrySeoul National UniversitySeoulRepublic of Korea Dental Research Institute and Dental Multi-omics center Seoul National UniversitySeoulRepublic of Korea Portrai Inc. SeoulRepublic of Korea Department of Surgery Yonsei University Health SystemYonsei University College of MedicineSeoulRepublic of Korea Department of Surgery Soonchunhyang Bucheon HospitalSoonchunhyang University College of MedicineBucheonRepublic of Korea

Gastric cancer(Gc)is a pervasive global malignancy with high mortality rates due to distant metastasis[1].Gc metastasis can occur via hematogenous route,peri-toneal route,and specifically through ovarian spread in females[2].Among these,peritoneal metastasis is the most prevalent and challenging condition to treat[3].The cancer Genome Atlas(TcGA)has uncovered four molec-ular subtypes of Gc:microsatellite instability,Epstein-Barr virus-related,chromosomal instability,and genomically stable[4].

关键词： metastasis peritoneal cancer

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Recent Advances in Nanoengineering of Electrode-Electrolyte Interfaces to Realize High-Performance Li-Ion Batteries

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Energy & Environmental Materials 2024年第3期7卷 1-13页

作者： Na-Yeong Kim Ilgyu Kim Behnoosh Bornamehr Volker Presser Hiroyuki Ueda Ho-Jin Lee Jun young cheong Ji-Won Jung School of Materials Science and Engineering University of UlsanTechno saneop-ro 55 beon-gilNam-guUlsan 44776Korea INM-Leibniz Institute for New Materials Campus D2266123Saarbrücken Germany Department of Materials Science and Engineering Campus D2266123Saarbrücken Germany saarene-Saarland center for Energy Materials and Sustainability Campus C4266123Saarbrücken Germany Institute for Frontier Materials(IFM) Deakin University221 Burwood HighwayBurwood Victoria 3125Australia Battery Research and Innovation Hub Deakin University5/154 Highbury RoadBurwood Victoria 3125Australia Bavarian center for Battery Technology(BayBatt)and Department of chemistry University of BayreuthUniversitatsstraBe 3095447Bayreuth Germany

A suitable interface between the electrode and electrolyte is crucial in achieving highly stable electrochemical performance for Li-ion batteries,as facile ionic transport is *** research and development have recently been conducted to form a stable interface between the electrode and ***,it is essential to investigate emerging knowledge and contextualize *** nanoengineering of the electrode-electrolyte interface has been actively researched at the electrode/electrolyte and interphase *** review presents and summarizes some recent advances aimed at nanoengineering approaches to build a more stable electrode-electrolyte interface and assess the impact of each approach ***,future perspectives on the feasibility and practicality of each approach will also be reviewed in ***,this review aids in projecting a more sustainable research pathway for a nanoengineered interphase design between electrode and electrolyte,which is pivotal for high-performance,thermally stable Li-ion batteries.

关键词： battery electrode electrolyte interface lithium nanoengineering

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Delphi study for developing a checklist of adverse events associated with acupotomy

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Journal of Integrative Medicine 2024年第5期22卷 579-587页

作者： Hyungsun Jun Haebeom Lee Sang-Hoon Yoon chan-young Kwon Damin Jeon Jun-Hwan Lee Jungtae Leem Department of Diagnostics College of Korean MedicineWonkwang UniversityIksan 54538Republic of Korea Days Inc. Seoul 06247Republic of Korea chung-Yeon Korean Medicine clinic Seoul 06224Republic of Korea Department of Oriental Neuropsychiatry Dong-Eui University College of Korean MedicineBusan 47227Republic of Korea chonnam National University Hwasun Hospital Hwasun 58128Republic of Korea KM Science Research Division Korea Institute of Oriental MedicineDaejeon 34054Republic of Korea Department of Korean convergence Medical Science KIOM SchoolUniversity of Science&Technology(UST)Daejeon 34054Republic of Korea Department of Physical Medicine and Rehabilitation Spaulding Rehabilitation HospitalHarvard Medical SchoolBostonMA 02115USA Research center of Traditional Korean Medicine College of Korean MedicineWonkwang UniversityIksan 54538Republic of Korea

Background Acupotomy,a more invasive procedure than acupuncture,involves the use of a thicker needle with an integrated knife at the tip,necessitating safety *** aimed to define relevant adverse events(AEs)and create a standardized form of the AcUPOtomy-related AEs cHEcKlist(AcUPOcHEcK).Methods Before conducting the Delphi process,a systematic review and pilot prospective study were conducted to gather information on previously reported *** these data,pilot versions of the AcUPOcHEcK and Delphi questionnaires were *** Delphi questionnaire involved selecting types of AE for inclusion,establishing separate criteria for acupotomy-related AEs,and achieving a consensus on AE *** Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi *** was considered to have been reached if the critical value for the content validity ratio met or exceeded *** The final AcUPOcHEcK was developed using four rounds of the Delphi method and one face-to-face consensus *** included 12 local AEs(pain,hemorrhage,bruise,hematoma,edema,pruritus,rash,infection,nerve damage,dysesthesia,movement impairment,and pneumothorax)and 14 systemic AEs(disease aggravation,needle fatigue,sleepiness,procedural nausea,procedural vomiting,procedural headache,procedural dizziness,sweating,procedural shock,syncope,dyspnea,procedural pain,sleep disorder,and postprocedural infection).Separate criteria were established for pain,hemorrhage and bruising:pain was defined as pain that occurrs during daily activities and persists for longer than 72 h,hemorrhage as bleeding that continues for≥3 min despite pressure application,and bruising as having a bruise with a diameter of≥3 ***-ended descriptions were allowed for AEs not covered by the checklist,and severity and causality were assessed using the common Terminology criteria for Adverse Events and modified World Health Organization-Uppsala Monitoring c

关键词： Acupotomy Delphi technique Patient safety Safety management Adverse event

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Low temperature-mediated repression and far-red light-mediated induction determine morning FLOWERING LOcUS T expression levels

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Journal of Integrative Plant Biology 2024年第1期66卷 103-120页

作者： Hayeon Kim Hye Won Kang Dae Yeon Hwang Nayoung Lee Akane Kubota Takato Imaizumi young Hun Song Department of Agricultural Biotechnology Seoul National UniversitySeoul 08826Korea Department of Biology Ajou UniversitySuwon 16499Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Korea Graduate School of Science and Technology Nara Institute of Science and TechnologyIkomaNara 630‐0192Japan Department of Biology University of WashingtonSeattleWA 98195USA Institute of Agricultural Life Sciences Seoul National UniversitySeoul 08826Korea

In order to flower in the appropriate season,plants monitor light and temperature changes and alter downstream pathways that regulate florigen genes such as Arabidopsis(Arabidopsis thaliana)FLOWERING LOcUS T(FT).In Arabidopsis,FT messenger RNA levels peak in the morning and evening under natural long-day conditions(LDs).However,the regulatory mechanisms governing morning FT induction remain poorly *** morning FT peak is absent in typical laboratory LDs characterized by high red:far-red light(R:FR)ratios and constant ***,we demonstrate that ZEITLUPE(ZTL)interacts with the FT repressors TARGET OF EATs(TOEs),thereby repressing morning FT expression in natural *** LDs with simulated sunlight(R:FR=1.0)and daily temperature cycles,which are natural LD-mimicking environmental conditions,FT transcript levels in the ztl mutant were high specifically in the morning,a pattern that was mirrored in the toe1 toe2 double *** night-to-morning temperatures increased the inhibitory effect of ZTL on morning FT expression by increasing ZTL protein levels early in the ***-red light counteracted ZTL activity by decreasing its abundance(possibly via phytochrome A(phyA))while increasing GIGANTEA(GI)levels and negatively affecting the formation of the ZTL-GI complex in the ***,the phyA-mediated high-irradiance response and GI play pivotal roles in morning FT *** findings suggest that the delicate balance between low temperature-mediated ZTL activity and the far-red light-mediated functions of phyA and GI offers plants flexibility in fine-tuning their flowering time by controlling FT expression in the morning.

关键词： far-red light FLOWERING LOcUS T flowering time GIGANTEA low night-to-morning temperature natural long days phytochrome A red to far-red ratio ZEITLUPE

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Programmable directional color dynamics using plasmonics

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Microsystems & Nanoengineering 2024年第1期10卷 325-334页

作者： Gyurin Kim Doeun Kim Soeun Ko Jang-Hwan Han Juhwan Kim Joo Hwan Ko young Min Song Hyeon-Ho Jeong School of Electrical Engineering and computer Science Gwangju Institute of Science and TechnologyGwangju 61005Republic of Korea Department of Semiconductor Engineering Gwangju Institute of Science and TechnologyGwangju 61005Republic of Korea Artificial Intelligence(AI)Graduate School Gwangju Institute of Science and TechnologyGwangju 61005Republic of Korea

Adaptive multicolor filters have emerged as key components for ensuring color accuracy and resolution in outdoor visual ***,the current state of this technology is still in its infancy and largely reliant on liquid crystal devices that require high voltage and bulky structural ***,we present a multicolor nanofilter consisting of multilayered‘active’plasmonic nanocomposites,wherein metallic nanoparticles are embedded within a conductive polymer *** nanocomposites are fabricated with a total thickness below 100 nm using a‘lithography-free’method at the wafer level,and they inherently exhibit three prominent optical modes,accompanying scattering phenomena that produce distinct dichroic reflection and transmission ***,a pivotal achievement is that all these colors are electrically manipulated with an applied external voltage of less than 1 V with 3.5 s of switching speed,encompassing the entire visible ***,this electrically programmable multicolor function enables the effective and dynamic modulation of the color temperature of white light across the warm-to-cool spectrum(3250 K-6250 K).This transformative capability is exceptionally valuable for enhancing the performance of outdoor optical devices that are independent of factors such as the sun’s elevation and prevailing weather conditions.

关键词： directional prevailing exceptional

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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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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 *** type 1 diabetes(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 by the EZH2 *** 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 *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** 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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