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The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

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Oncology Research 2024年第7期32卷 1231-1237页

作者： MOHAMMAD-TAGHI MORADI DHIYA ALTEMEMY MAJID ASADI-SAMANI PEGAH KHOSRAVIAN MARZIYEH SOLTANI LEILA HASHEMI AZADEH SAMIEI-SEFAT Medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran department of Pharmaceutics College of PharmacyAl-Zahraa University for WomenKarbalaIraq cellular and molecular Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran

Background:Despite the availability of chemotherapy drugs such as 5-ﬂuorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side *** study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their *** proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)*** synergistic effect of 5-FU and celastrol was studied using Compusyn *** DNA content at different phases of the cell cycle and apoptosis rate was measured usingﬂow ***:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU signiﬁcantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,*** mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,*** addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis ***:Although celastrol could decrease the concentration of 5-ﬂuorouracil that sufﬁced to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

关键词： Gastric cancer Celastrol Terpenoid Cell cycle regulation Apoptosis Synergism

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Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin Lim department of Biochemistry&molecular biology Ajou University School of MedicineSuwonSouth Korea department of Biomedical Sciences Graduate School of Ajou UniversitySuwonSouth Korea department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

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Acoustical properties of a 3D printed honeycomb structure filled with nanofillers:Experimental analysis and optimization for emerging applications

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Defence Technology（防务技术） 2024年第5期35卷 248-258页

作者： Jeyanthi Subramanian Vinoth kumar Selvaraj Rohan Singh Ilangovan S Naresh Kakur Ruban Whenish School of Mechanical Engineering Vellore Institute of TechnologyChennai600127Tamil NaduIndia department of Mechanical Engineering SRM Institute of Science and TechnologyRamapuramChennai600089India department of Chemical Engineering and Materials Science University of Southern CaliforniaLos Angeles90089USA Advanced Materials Research Centre Technology Innovation InstituteAbu Dhabi9639UAE Center for Biomaterials Cellular and Molecular TheranosticsVellore Institute of TechnologyVellore632014Tamil NaduIndia

The novelty of this research lies in the successful fabrication of a 3D-printed honeycomb structure filled with nanofillers for acoustic properties,utilizing an impedance tube setup in accordance with ASTM standard E *** Creality Ender-3,a 3D printer,was used for printing the honeycomb structures,and polylactic acid(PLA)material was employed for their *** organic,inorganic,and polymeric compounds within the composites were identified using fourier transformation infrared(FTIR)*** structure and homogeneity of the samples were examined using a field emission scanning electron microscope(FESEM).To determine the sound absorption coefficient of the 3D printed honeycomb structure,numerous samples were systematically developed using central composite design(CCD)and analysed using response surface methodology(RSM).The RSM mathematical model was established to predict the optimum values of each factor and noise reduction coefficient(NRC).The optimum values for an NRC of 0.377 were found to be 1.116 wt% carbon black,1.025 wt% aluminium powder,and 3.151 mm distance between parallel ***,the results demonstrate that a 3Dprinted honeycomb structure filled with nanofillers is an excellent material that can be utilized in various fields,including defence and aviation,where lightweight and acoustic properties are of great importance.

关键词： 3D printing Honeycomb structure Acoustics Field emission scanning electron microscope Response surface methodology

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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is en

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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Angiosperm-wide analysis of fruit and ovary evolution aided by a new nuclear phylogeny supports association of the same ovary type with both dry and fleshy fruits

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Journal of Integrative Plant biology 2024年第2期66卷 228-251页

作者： Yezi Xiang Taikui Zhang Yiyong Zhao Hongjin Dong Hongyi Chen Yi Hu Chien-Hsun Huang Jun Xiang Hong Ma State Key Laboratory of Genetic Engineering Ministry of Education Key Laboratory of Biodiversity and Ecological EngineeringInstitute of Plant BiologyCenter of Evolutionary BiologySchool of Life SciencesFudan UniversityShanghai 200438China department of biology Howard Hughes Medical InstituteDuke UniversityDurhamNC 27708USA department of biology the Eberly College of Scienceand the Huck Institutes of the Life Sciencesthe Pennsylvania State UniversityUniversity ParkPA 16802USA Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization College of Biology and Agricultural ResourcesHuanggang Normal UniversityHuanggang 438000China

Fruit functions in seed protection and dispersal and belongs to many dry and fleshy types,yet their evolutionary pattern remains unclear in part due to uncertainties in the phylogenetic relationships among several orders and *** we used nuclear genes of 502 angiosperm species representing 231 families to reconstruct a well supported phylogeny,with resolved relationships for orders and families with previously uncertain *** this phylogeny as a framework,molecular dating supports a Triassic origin of the crown angiosperms,followed by the emergence of most orders in the Jurassic and Cretaceous and their rise to ecological dominance during the Cretaceous Terrestrial *** robust phylogeny allowed an examination of the evolutionary pattern of fruit and ovary types,revealing a trend of parallel carpel fusions during early diversifications in eudicots,monocots,and ***,taxa in the same order or family with the same ovary type can develop either dry or fleshy fruits with strong correlations between specific types of dry and fleshy fruits;such associations of ovary,dry and fleshy fruits define several ovaryfruit"modules"each found in multiple *** of the frequent modules has an ovary containing multiple ovules,capsules and berries,and another with an ovary having one or two ovules,achenes(or other single-seeded dry fruits)and *** new perspective of relationships among fruit types highlights the closeness of specific dry and fleshy fruit types,such as capsule and berry,that develop from the same ovary type and belong to the same module relative to dry and fleshy fruits of other modules(such as achenes and drupes).Further analyses of gene families containing known genes for ovary and fruit development identified phylogenetic nodes with multiple gene duplications,supporting a possible role of whole-genome duplications,in combination with climate changes and animal behaviors,in angiosperm fruit and ovary diversificat

关键词： angiosperm fruit evolution MADS-box molecular clock nuclear phylogeny ovary and fruit developmental genes

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang department of molecular Cell biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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Zoonotic human liver flukes, a type 1 biocarcinogen, in freshwater fishes: genetic analysis and confirmation of molluscan vectors and reservoir hosts in Bangladesh

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贫困所致传染病(英文) 2024年第3期13卷 1-16页

作者： Labony Sharmin Shahid Alim Md. Abdul Hasan Muhammad Mehedi Hossain Md. Shahadat Akter Sharmin Paul Joydeep Farjana Thahsin Ali Md. Haydar Alam Mohammad Zahangir Hatta Takeshi Kawada Hayato Mizutani Keiko Tsuji Naotoshi Anisuzzaman department of Parasitology Faculty of Veterinary Science Bangladesh Agricultural University Mymensingh Bangladesh department of Fisheries Technology Faculty of Fisheries Bangladesh Agricultural University Mymensingh Bangladesh department of Biotechnology School of Life Sciences &amp Biotechnology Adamas University Barasat - Barrackpore Rd Jagannathpur Kolkata West Bengal India department of Pathology and Parasitology Hajee Mohammad Danesh Science and Technology University Dinajpur Bangladesh department of Parasitology and Tropical Medicine Kitasato University School of Medicine-15-Kitasato Minami Sagamihara Kanagawa-0374 Japan department of molecular and cellular Parasitology Kitasato University Graduate School of Medical Sciences-15-Kitasato Minami Sagamihara Kanagawa-0373 Japan

Background Opisthorchiid flukes, particularlyOpisthorchis viverrini,Opisthorchis felineus,Clonorchis sinensis, andMetorchis spp. are the most common fish-borne zoonotic human liver flukes (hLFs). Liver fluke infections are more prevalent in resource-deprived and underprivileged areas. We herein estimated the prevalence of the metacercariae (MC) of major hLFs in common large freshwater fishes (lFWF) marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and *** The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018–June 2022 using conventional and multiple molecular techniques, such as PCR, PCR-restriction fragment length polymorphism (RFLP), sequencing, and bioinformatic analyses. The infection rate of fishes was analyzed using theZ-test and the loads of MC were compared using the chi-squared (χ2) *** The MC ofC. sinensis,Opisthorchis spp., andMetorchis spp. were detected in 11 species of common and popular lFWF. In lFWF, the estimated prevalence was 18.7% and the mean load was 137.4 ± 149.8 MC per 100 g of fish. The prevalence was the highest (P 0.05) distributed between the head and body of fishes. The infection rate was slightly higher in cultured (19.6%) fishes. The MC ofC. sinensis,O. felineus,O. viverrini, andMetorchis orientalis in fishes were confirmed using PCR, PCR-RFLP and bioinformatics. The cercariae of opisthorchiid (Pleurolophocercus cercariae) flukes were only recovered fromBithynia spp. (3.9%, 42 out of 1089). The ova of hLFs from dogs (4.3%, 5 out of 116) and cats (6.0%, 6 out of 100), and adult flukes (***) from ducks

关键词： Human liver fluke Freshwater fish Molluscan vector Reservoir host Bangladesh

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RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila

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Marine Life Science & Technology 2024年第2期6卷 183-197页

作者： Huijuan Hao Yinjie Lian Chenhui Ren Sitong Yang Min Zhao Tao Bo Jing Xu Wei Wang Key Laboratory of Chemical biology and molecular Engineering of Ministry of Education Institute of BiotechnologyShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China Shanxi Key Laboratory of Biotechnology Taiyuan 030006China

Histone modification and nucleosome assembly play important roles in chromatin-related *** chaperones form different complexes and coordinate histone transportation and *** histone chaperone complexes have been identified in different *** ciliate protozoa(ciliates)have various chromatin structures and different nuclear ***,histone chaperone components and functions of different subunits remain unclear in ***-rahymema thermophila contains a transcriptionally active macronucleus(MAC)and a transcriptionally inactive micronu-cleus(MIC)which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental ***,we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental ***1 knockdown inhibited cellular *** macronuclear morphology became bigger in growing *** abnormal macronuclear structure also occurred in the starvation ***,micronuclear meiosis was disturbed during sexual development,leading to a failure to generate new gametic ***1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental ***1 knockdown affected expression levels of the genes involved in chromatin organization and *** together,RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in ***.

关键词： Gametogenesis Histone chaperone Macronuclear structure RebL1 Tetrahymena thermophilaIntroduction

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Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

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Nano Research 2024年第7期17卷 6386-6399页

作者： Jun Zhu Shoujie Zhao Yejing Zhu Shouzheng Ma Tenghui Han Fenghua Xu Huichen Li Bo Wang Zhixiong Guo Da Chen Yongquan Qu Zhimin Tian Junlong Zhao Lei Liu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers National Clinical Research Center for Digestive DiseasesXijing HospitalFourth Military Medical UniversityXi’an 710032China department of General Surgery The Southern Theater Air Force HospitalGuangzhou 510602China department of General Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China department of Thoracic Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China department of Neurology Airborne Army HospitalWuhan 430012China Key Laboratory of Modern Teaching Technology(Ministry of Education) Shaanxi Normal UniversityXi’an 710062China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China department of Pediatrics Tangdu HospitalFourth Military Medical UniversityXi’an 710000China

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate ***,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to *** this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of ***,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal *** prominent ferroptosis biomarkers,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ***,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@*** orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@*** conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

关键词： anti-tumor ferroptosis Fe-Material of Institut Lavoisier(Fe-MIL) sorafenib adenosine monophosphate(AMP)-activated protein kinase(AMPK)

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Two MADS-box proteins,AGL9 and AGL15,recruit the FIS-PRC2 complex to trigger the phase transition from endosperm proliferation to embryo development in Arabidopsis

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molecular Plant 2024年第7期17卷 1110-1128页

作者： Shen Zhang Devasantosh Mohanty Adnan Muzaffar Min Ni department of Plant and Microbial biology University of Minnesota at Twin CitiesSaint PaulMinnesota MN 55108United States of AmericaUSA

Spatiotemporal regulation of gene expression by polycomb repressive complex 2(PRc2)is critical for animal and plant *** Arabidopsis fertilization independent seed(FIS)-PRC2 complex functions specifically during plant reproduction from gametogenesis to seed *** a double fertilization event,triploid endosperm proliferates early,followed by the growth of a diploid embryo,which replaces the endosperm in Arabidopsis and many *** genes critical for endosperm proliferation such as IKkU2 and MINI3 are activated after *** we report that two MADS-box AGAMOUS-LIKE(AGL)proteins associate with the key endosperm proliferation loci and recruit the FIS-PRC2 repressive complex at 4-5 days after pollination(DAP).Interestingly,AGL9 and AGL15 only accumulate toward the end of endosperm proliferation at 4-5 DAP and promote the deposition of H3K27me3 marks at key endosperm proliferation *** of AGL9 and AGL15 or overexpression of AGL9 or AGL15 significantly influence endosperm proliferation and ***-wide analysis with cleavage Under Targets and tagmentation(CUT&Tag)sequencing and RNA sequencing revealed the landscape of endosperm H3K27me3 marks and gene expression profiles in Col-0 and agl9 ***&Tag qPCR also demonstrated the occupancy of the two MADS-box proteins and FIS-PRC2 on a few representative target *** studies suggest that MADS-box proteins could potentially recruit PRc2 to regulate many other developmental processes in plants or even in fungi and animals.

关键词： AGL9 AGL15 embryo endosperm IKU2 MEDEA MINI3

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