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RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew small Jianhuang Xue Huilin Huang Hengyou Weng Rui su brandon Tan Chao shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate school of Biological sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family Center for Leukemia Research City of HopeDuarteCA 91010USA sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China school of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

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Natural rubber and the Russian dandelion genome

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National science Review 2018年第1期5卷 88-89页

作者： brandon s.Gaut Department of Ecology and Evolutionary Biology University of California

The world needs *** is crucial for the tires on the cars,trucks and airplanes that propel modern *** is equally important for daily tasks:latex gloves in the lab,balloons in angioplasty and wetsuits that warm a cold dip in the *** can be made synthetically from petroleum derivatives,but synthetic rubber is not as strong as rubber isolated from *** principal plant source for natural rubber

关键词： Natural rubber and the Russian dandelion genome

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Focus on current and emerging treatment options for glioma:A comprehensive review

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World Journal of Clinical Oncology 2024年第4期15卷 482-495页

作者： brandon Lucke-Wold Burhanuddin sohail Rangwala Muhammad Ashir shafique Mohammad Arham siddiq Muhammad saqlain Mustafa Fnu Danish Rana Muhammad Umer Nasrullah Noor Zainab Abdul Haseeb Department of Neurosurgery University of FloridaGainesvilleFL 32608United States Department of Neurosurgery Jinnah Sindh Medical UniversityKarachi 75510Pakistan Department of Neurosurgery Army Medical CollegeRawalpindi 46000Pakistan

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas(LGG),the predominant primary tumors in the central nervous *** a general incidence rate of 5.81 per 100000,gliomas pose a significant global concern,necessitating advancements in treatment techniques to reduce mortality and *** review places a particular focus on immunotherapies,discussing promising agents such as Zotiraciclib and ***,a CDK9 inhibitor,has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies,showing its potential as a therapeutic ***,a viral immunotherapy,induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric *** of immunotherapy extends to Pembrolizumab,Nivolumab,and Entrectinib,revealing the challenges and variabilities in patient *** promising preclinical data,the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment,emphasizing the critical need to understand resistance *** review also covers the success of radiation therapy in pediatric LGG,with evolving techniques,such as proton therapy,showing potential improvements in patient quality of *** treatment is discussed in the context of achieving a balance between preserving the patient’s quality of life and attaining gross total resection,with the extent of surgical resection significantly influencing the survival *** addition to advancements in cancer vaccine development,this review highlights the evolving landscape of LGG treatment,emphasizing a shift toward personalized and targeted *** research is essential for refining strategies and enhancing outcomes in the management of LGG.

关键词： Low-grade gliomas Monoclonal antibody Lerapolturev Glioblastoma CDK9 inhibitor

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Theory, simulation and experiment of optical properties of cobalt ferrite(CoFe2O4) nanoparticles

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Journal of Materials science & Technology 2020年第22期54卷 180-187页

作者： Elham Gharibshahi brandon D.Young Amar s.Bhalla Ruyan Guo Department of Electrical and Computer Engineering University of Texas at San Antonio.One UTSA CircleSan AntonioTX 78249USA

Optical properties of cobalt ferrite(CoFe2O4) nanoparticles are modeled and simulated employing finite element analysis(FEA) and density functional theory(DFT) for different particle sizes. The simulated absorption maxima of electronic excitations is red-shifted from 330 nm to 410 nm using finite element analysis and from 331.27 nm to 409.07 nm using quantum mechanical method, with increasing particle sizes from 40 nm to 50 nm. The measured absorption maxima matched the simulated results reasonably well and red-shifted to longer wavelengths from 315.59 nm to 426.73 nm with the increase in particle sizes from 30 nm to 50 nm. The DFT simulated, FEA simulated and experimentally derived optical band gap energies, Eg, were also acquired and compared. The simulated Egvalues decreased from 3.228 to 2.478 e V and from 3.266 to 2.456 e V, while the experimental Egvalue decreased from 3.473 to 2.697 e V, with increasing the particle sizes. The research demonstrated that the optical absorption of CoFe2O4 nanoparticles can be described with high accuracy using the quantum mechanical interpretation based on DFT. FEA based simulations have shown limitations for smaller(s likely due to the increased surface scattering that prevented a stable solution for simulations beyond the quasistatic limit. The DFT computational tool developed by this study can enable both the low cost computation and highly reliable prediction of optical absorption properties and optical band edges, and thus contribute to understanding and design of CoFe2O4 nanoparticle properties prior to fabrication and functionalization of them, for a wide range of applications especially for sensing and photonic wave modulations.

关键词： Cobalt ferrite(CoFe2O4)nanoparticles Optical properties Band gap energy DFT simulation of nanoparticles COMsOL simulation of nanoparticles

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Gene capture by transposable elements leads to epigenetic conflict in maize

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Molecular Plant 2021年第2期14卷 237-252页

作者： Aline Muyle Danelle seymour Nikos Darzentas Elias Primetis brandon s.Gaut Alexandros Bousios Department of Ecology and Evolutionary Biology UC IrvineIrvineCA 92697USA Department of Botany and Plant sciences UC RiversideRiversideCA 92521USA Central European Institute of Technology Masaryk UniversityBrnoCzech Republic school of Life sciences University of SussexBrightonUK

Transposable elements(TEs)regularly capture fragments of *** the host silences these TEs,siRNAs homologous to the captured regions may also target the *** epigenetic crosstalk establishes an intragenomic conflict:silencing the TEs has the cost of silencing the *** genes are important,however,natural selection may maintain function by moderating the silencing response,which may also advantage the *** this study,we examined this model by focusing on Helitrons,Pack-MULEs,and sirevirus LTR retrotransposons in the maize *** documented 1263 TEs containing exon fragments from 1629 donor *** with epigenetic conflict,donor genes mapped more siRNAs and were more methylated than genes with no evidence of ***,these patterns differed between syntelog versus translocated donor *** appeared to maintain function,as measured by gene expression,consistent with moderation of silencing for functionally important *** marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH *** genes,in contrast,bore the signature of *** were highly methylated and less expressed,but also overrepresented among donor genes and located away from chromosomal arms,which suggests a link between capture and gene *** genes into potential functional categories based on evolutionary constraint supported the synteny-based *** families captured genes in different ways,but the evidence for their advantage was generally less obvious;nevertheless,TEs with captured fragments were older,mapped fewer siRNAs,and were slightly less methylated than TEs without captured ***,our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.

关键词： transposable elements intragenomic conflict gene capture epigenetic silencing methylation synteny

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Male Burmese pythons follow female scent trails and show sex-specific behaviors

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Integrative Zoology 2019年第5期14卷 460-469页

作者： shannon A.RICHARD Eric A.TILLMAN John s.HUMPHREY Michael L.avery M.Rockwell PARKER Department of Biology James Madison UniversityHarrisonburgVirginiaUSA National Wildlife Research Center Florida Field StationU.S.Department of AgricultureGainesvilleFloridaUSA

Animals communicate with potential mates using species-specific signals,and pheromones are powerful sexual signals that modify conspecific behavior to facilitate mate *** the vertebrates,snakes are especially adept in mate searching via chemical trailing,which is particularly relevant given that many snake species are invasive outside their native *** signals used in mate choice are,thus,potentially valuable tools for management of invasive snake *** Burmese python(Python bivittatus)is an invasive snake in the Florida Everglades where it is negatively impacting native *** this study,we sought to:(i)determine if males can follow conspecific chemical trails in a Y-maze;and(ii)describe the mate searching behaviors exhibited by males while *** males consistently followed a single female scent trail in the maze,but when only a male scent trail was present they did not discriminate between the male and blank *** of tongue-flicking,a proxy for chemosensory sampling,was also marginally higher when males were following female versus male scent ***,when both female and male scent trails were simultaneously present in the Y-maze,males did not show a preference for the female arm,although the tongue-flick rate was higher in the female-only trial compared to female versus *** of multiple male behaviors individually and using an ethogram revealed that behaviors were more frequent and complex in the female-only trials compared to male-only *** behavioral trials are needed to determine if an effective pheromonal approach to Burmese python management is possible.

关键词： chemical ecology invasive species pheromone snake trailing

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Eccentric exercise-induced muscle weakness abolishes sex differences in fatigability during sustained submaximal isometric contractions

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运动与健康科学(英文) 2023年第4期12卷 523-533页

作者： Hanna L.Jodoin avery Hinks Olivia P.Roussel Vincenzo s.Contento Brian H.Dalton Geoffrey A.Power Department of Human Health and Nutritional sciences College of Biological SciencesUniversity of GuelphGuelphON N1G 2W1Canada school of Health and Exercise science University of British ColumbiaKelownaBC V1V 1V7Canada

Background:Females are typically less fatigable than males during sustained isometric contractions at lower isometric contraction *** sex difference in fatigability becomes more variable during higher intensity isometric and dynamic *** less fatiguing than isometric or concentric contractions,eccentric contractions induce greater and longer lasting impairments in force ***,it is not clear how muscle weakness influences fatigability in males and females during sustained isometric ***:We investigated the effects of eccentric exercise-induced muscle weakness on time to task failure(TTF)during a sustained submaximal isometric contraction in young(18-30 years)healthy males(n=9)and females(n=10).Participants performed a sustained isometric contraction of the dorsiflexors at 35°plantar flexion by matching a 30%maximal voluntary contraction(MVC)torque target until task failure(i.e.,falling below 5%of their target torque for>2 s).The same sustained isometric contraction was repeated 30 min after 150 maximal eccentric *** and antagonist activation were assessed using surface electromyography over the tibialis anterior and soleus muscles,***:Males were~41%stronger than *** eccentric exercise both males and females experienced an~20%decline in maximal voliuntary contraction *** was-34%longer in females than males prior to eccentic exercise-induced muscle ***,following eccentric exercise-induced muscle weakness,this sex-related difference was abolished,with both groups having an"45%shorter ***,there was~100%greater antagonist activation in the female group during the sustained isometric contraction following exercise-induced weakness as compared to the ***:This increase in antagonist activation disadvantaged females by decreasing their TTF,resulting in a blunting of their typical fatigability advantage over males.

关键词： Fatigue Isometric sex Time to task failure Weakness

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Multifunctional to multistage delivery systems: The evolution of nanoparticles for biomedical applications

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Chinese science Bulletin 2012年第31期57卷 3961-3971页

作者： MARTINEZ Jonathan O BROWN brandon s QUATTROCCHI Nicoletta EVANGELOPOULOs Michael FERRARI Mauro TAsCIOTTI Ennio Department of Nanomedicine The Methodist Hospital Research Institute Graduate school of Biomedical sciences The University of Texas at Houston

Nanomaterials are advancing in several directions with significant progress being achieved with respect to their synthesis, functionalization and biomedical application. In this review, we will describe several classes of prototypical nanocarriers, such as liposomes, silicon particles, and gold nanoshells, in terms of their individual function as well as their synergistic use. Active and passive targeting, photothermal ablation, and drug controlled release constitute some of the crucial functions identified to achieve a medical purpose. Current limitations in targeting, slow clearance, and systemic as well as local toxicity are addressed in reference to the recent studies that attempted to comprehend and solve these issues. The demand for a more sophisticated understanding of the impact of nanomaterials on the body and of their potential immune response underlies this discussion. Combined components are then discussed in the setting of multifunctional nanocarriers, a class of drug delivery systems we envisioned, proposed, and evolved in the last 5 years. In particular, our third generation of nanocarriers, the multistage vectors, usher in the new field of nanomedicine by combining several components onto multifunctional nanocarriers characterized by emerging properties and able to achieve synergistic effects.

关键词：生物医学应用纳米粒子多功能传递系统演变多级药物控制释放纳米载体

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Microstructure, precipitates and mechanical properties of powder bed fused inconel 718 before and after heat treatment

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Journal of Materials science & Technology 2019年第6期35卷 1153-1164页

作者： Le Zhou Abhishek Mehta brandon McWilliams Kyu Cho Yongho sohn Advanced Materials Processing and Analysis Center University of Central Florida Orlando FL 32816 USA Department of Materials science and Engineering University of Central Florida Orlando FL 32816 USA Weapons and Materials Research Directorate US. Amy Research Laboratory Aberdeen Proving Ground MD 21005 USA

IN718 alloy was fabricated by laser powder bed fusion(PBF) for examination of microstructure, precipitates and mechanical properties in the as-built state and after different heat treatments. The as-built alloy had a characteristic fine cellular-dendritic microstructure with Nb, Mo and Ti segregated along the interdendritic region and cellular boundary. The as-built alloys were then subjected to solution heat treatment(sHT) at 980°C or 1065°C for 1 h. sHT at 980°C led to the formation of δ-phase in the interdendritic region or cellular boundary. The segregation was completely removed by the sHT at 1065°C, but recrystallization was observed, and the carbides decorated along the grain boundaries. The as-built alloy and alloys with sHT at 980°C and 1065°C were two-step aged, which consisted of annealing at 720°C for8 h followed by annealing at 620°C for 8 h. Transmission electron microscopy revealed the precipitation of λ’ and λ" in all alloys after two-step aging, but the amount and uniformity of distribution varied. The Vickers hardness of the PBF IN718 alloy increased from 296 HV to 467 HV after direct aging. The hardness decreased to 267 HV and 235 HV after sHT at 980°C and 1065°C, respectively, but increased to 458 HV and 477 HV followed by aging. The evolution of Young’s modulus after heat treatment exhibited similar trend to that of hardness. The highest hardness was observed for IN718 after sHT at 1065°C and two-step aging due to precipitation with greater amount and uniform distribution.

关键词： Laser powder bed fusion IN718 Microstructure Transmission electron microscopy

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Redefining Human Vitamin D sufficiency:Back to the Basics

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Bone Research 2013年第1期1卷 2-10页

作者： John s.Adams Jonathan Ramin brandon Rafison Charles Windon Annika Windon Philip T.Liu Orthopaedic Hospital Research Center UCLA-Orthopaedic Hospital Department of Orthopaedic SurgeryDavid Geffen School of MedicineUCLA Department of Molecular Cell and Developmental BiologyDivision of Life SciencesCollege of Letters and ScienceUCLA

The role of the endocrine vitamin D pathway in regulating the serum calcium concentration in man is well described. In the presence of a low serum calcium level, the vitamin D metabolic pathway is called upon to produce more of the active vitamin D hormone, 1, 25-dihydroxyvitamin D （1, 25D）, via up-regulation of the CYP27b1-hydroxylase activity in the kidney. The consequence is mobilization of skeletal calcium stores to return the circulating calcium level back to the normal range. On the other hand, when the serum calcium level increases, endocrine forces move to suppress renal 1, 25D production and squelch bone resorption. It is now known that vitamin D metabolites also operate in an autocrine, paracrine and intracrine mode to control vitamin D receptor-directed biological responses at the tissue level. Because the metabolism and action of vitamin D occurs at the tissue level in this situation, use of circulating vitamin D metabolites and biomarkers to ascertain the local action of the vitamin D pathway is often misleading. This mini-review seeks to compare and contrast the operation of the vitamin D pathway at the endocrine and tissue level.

关键词： metabolism endocrine autocrine hormone biomarkers

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