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The em.rging role and targetability of the TCA cycle in cancer m.tabolism

Protein & Cell 2018年第2期9卷 216-237页

作者： nicole m. anderson Patrick m.cka Joseph G. Kern Hui Feng Abram.on Fam.ly Cancer Research Institute University of Pennsylvania Philadelphia PA 19104-6160 USA Perelm.n School of m.dicine at the University of Pennsylvania Philadelphia PA 19104 USA Departm.nts of Pharm.cology and m.dicine The Center for Cancer Research Section of Hematology and Medical Oncology Boston University School of Medicine Boston MA 02118 USA Program.in Biom.dical Sciences Boston University School of Medicine Boston MA 02118 USA

The tricarboxylic acid （TCA） cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance require- m.nts. Despite early dogm. that cancer cells bypass the TCA cycle and prim.rily utilize aerobic glycolysis, em.rging evidence dem.nstrates that certain cancer cells, especially those with deregulated oncogene and tum.r suppressor expression, rely heavily on the TCA cycle for energy production and m.crom.lecule synthesis. As the field progresses, the im.ortance of aberrant TCA cycle function in tum.rigenesis and the potentials of applying sm.ll m.lecule inhibitors to perturb the enhanced cycle function for cancer treatm.nt start to evolve. In this review, we sum.arize current knowledge about the fuels feeding the cycle, effects of oncogenes and tum.r suppressors on fuel and cycle usage, com.on genetic alterations and deregulation of cycle enzym.s, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo m.del organism.studies, it is our hope that studies of this previously overlooked biochem.cal hub will provide fresh insights into cancer m.tabolism.and tum.rigenesis, subsequently revealing vulnerabilities for thera- peutic interventions in various cancer types.

关键词： glutam.nolysis the TCA cycle cancer m.tabolism glycolysis

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Controlling Heat Transfer for the m.nufacturing of High m.lecular Weight Polyisobutylene via Form.tion of m.celles

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Chinese Journal of Polym.r Science 2019年第9期37卷 898-902页

作者： Szilard Csihony nicole Janssen Klaus m.hlbach Advanced m.terials & System.

An alternative cationic polym.rization m.thod is developed to produce high m.lecular weight polyisobutylene (Hm.PIB) with m.lecular weights above 5×10^5g/m.l. The m.thod involves m.celle form.tion via functionalized low m.lecular weight polyisobutylene (Lm.PIB) in non-polar solvent. One end of Lm.PIB is m.dified with an im.dazolium.containing ionic group, which together with the anion (eg. Al2Cl7) works as Lewis acid. While the m.nom.r isobutylene dissolves readily in non-polar solvent, polym.rization can occur only within the m.celle, which affords stable Hm.PIB particles. Hm.PIB with a m.lecular weight (m.) close to 1 × 10^6 g/m.l was produced successfully with the described m.thod.

关键词： Cationic polym.rization High m.lecular weight polyisobutylene m.celle

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Future challenges in the in vitro and in vivo evaluation of biom.terial biocom.atibility

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Regenerative Biom.terials 2016年第2期3卷 73-77页

作者： Jam.s m.anderson Case Western Reserve University 2103 Cornell RoadWRB 5105ClevelandOH 44106-7288USA

As the science and engineering of biom.terials continues to expand with increased em.hasis on the developm.nt of nanom.terials and tissue engineering scaffolds,em.hasis also m.st be placed on appropriate and adequate approaches to the in vivo and in vitro evaluation of biom.terial biocom.atibility/biological response *** article presents six topic areas that should be addressed by investigators as they m.ve forward in the developm.nt of new system. for regenerative *** certainly,there are other areas that require attention to detail and a m.re com.lete understanding of the strengths and weaknesses of various experim.ntal approaches to biom.terial/biological response *** sm.ll num.er of issues addressed in this article is only m.ant to bring to the attention of prospective investigators and authors,the im.ortance of the developm.nt of adequate and appropriate evaluation techniques that address the unique features of biom.terials utilized in the developm.nt of new m.dical devices.

关键词： biom.terials nanom.terials tissue engineering

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How We Will Discover Sentience in AI

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Journal of Social Com.uting 2023年第3期4卷 181-192页

作者： m.rc m.anderson the LORIA UMR 7503Universitéde LorraineInria the CNRS Vandoeuvre-lès-Nancy 54506France

This paper explores the question of how we can know if Artificial Intelligence(AI)system. have becom. or are becom.ng *** an overview of som. argum.nts regarding AI sentience,it proceeds to an outline of the notion of negation in the philosophy of Josiah Royce,which is then applied to the argum.nts already ***’s notion of the prim.tive dyadic and sym.etric negation relation is shown to bypass such *** negation relation and its expansion into higher types of order are then considered with regard to how,in sm.ll variations of active negation,they would disclose sentience in AI ***,I argue that the m.ch-hyped argum.nts and apocalyptic speculations regarding Artificial General Intelligence(AGI)takeover and sim.lar scenarios,abetted by the notion of unlim.ted data,are based on a fundam.ntal m.sunderstanding of how entities engage their ***,lim.tation,proceeding from.the sym.etric negation relation,expands outward into higher types of order in polyadic relations,wherein the entity self-lim.ts and creatively m.ves toward uniqueness.

关键词： artificial intelligence sentience consciousness negation Josiah Royce logic Artificial General Intelligence(AGI)

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The role of cellular and m.lecular neuroim.une crosstalk in gut im.unity

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Cellular & m.lecular Im.unology 2023年第11期20卷 1259-1269页

作者： Daping Yang nicole Alm.nzar Isaac m.Chiu Departm.nt of Im.unology Harvard Medical SchoolBostonMA02115USA

The gastrointestinal tract is densely innervated by the peripheral nervous system.and populated by the im.une *** two system. critically coordinate the sensations of and adaptations to dietary,m.crobial,and dam.ging stim.li from.the external and internal m.croenvironm.nt during tissue hom.ostasis and *** brain receives and integrates ascending sensory signals from.the gut and transduces descending signals back to the gut via autonom.c *** regulate intestinal im.une responses through the action of local axon reflexes or through neuronal circuits via the gut-brain *** neuroim.une crosstalk is critical for gut hom.ostatic m.intenance and disease *** this review,we discuss the roles of distinct types of gut-innervating neurons in the m.dulation of intestinal m.cosal *** will focus on the m.lecular m.chanism. governing how different im.une cells respond to neural signals in host defense and *** also discuss the therapeutic potential of strategies targeting neuroim.une crosstalk for intestinal diseases.

关键词： Neuroim.unology Neuroim.une Host defense Gut Sensory

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Helper T cell differentiation

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Cellular & m.lecular Im.unology 2019年第7期16卷 634-643页

作者： Jordy Saravia nicole m.Chapm.n Hongbo Chi Departm.nt of Im.unology St.Jude Children’s Research HospitalMemphisTNUSA

CD4^(+)T helper cells are key regulators of host health and *** the original m.del,specialized subsets of T helper cells are generated following activation through lineage-specifying cytokines and transcriptional program.,but recent studies have revealed increasing com.lexities for CD4^(+)T-cell ***,we first discuss CD4^(+)T-cell differentiation from.a historical perspective by highlighting the m.jor studies that defined the distinct subsets of T helper *** next describe the m.chanism. underlying CD4^(+)T-cell differentiation,including cytokine-induced signaling and transcriptional *** then review current and em.rging topics of differentiation,including the plasticity and heterogeneity of T cells,the tissue-specific effects,and the influence of cellular m.tabolism.on cell fate ***,recent advances in cutting-edge approaches,especially system. biology tools,have contributed to new concepts and m.chanism. underlying T-cell differentiation and will likely continue to advance this im.ortant research area of adaptive im.unity.

关键词： T cells Treg differentiation plasticity im.unom.tabolism

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Pre-m.NA m.difications and their role in nuclear processing

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Frontiers of Electrical and Electronic Engineering in China 2018年第3期6卷 210-227页

作者： nicole m.m.rtinez Wendy V Gilbert Departm.nt of m.lecular Biophysics ＆ Biochem.stry Yale UniversityNew HavenCT 06520USA

Background： Cellular non-coding RNAs are extensively m.dified post-transcriptionally, with m.re than 100 chem.cally distinct nucleotides identified to date. In the past five years, new sequencing based m.thods have revealed widespread decoration of eukaryotic m.ssenger RNA with diverse RNA m.difications whose functions in m.NA m.tabolism.are only beginning to be known. Results： Since m.st of the identified m.NA m.difying enzym.s are present in the nucleus, these m.difications have the potential to function in nuclear pre-m.NA processing including alternative splicing. Here we review recent progress towards illum.nating the role of pre-m.NA m.difications in splicing and highlight key areas for future investigation in this rapidly growing field. Conclusions： Future studies to identify which m.difications are added to nascent pre-m.NA and to interrogate the direct effects of individual m.difications are likely to reveal new m.chanism. by which nuclear pre-m.NA processing is regulated.

关键词： m.NA m.dification pre-m.NA m.dification splicing RNA-m.difying enzym.s

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Borderline resectable pancreatic cancer: Definitions and m.nagem.nt

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World Journal of Gastroenterology 2014年第31期20卷 10740-10751页

作者： nicole E Lopez Cristina Prendergast Andrew m.Lowy Division of Surgical Oncology Department of Surgery Moores Cancer Center University of California San Diego

Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection rem.ins the only curative option, m.re than 80% of patients present with unresectable disease. Unfortunately, even am.ng those who undergo resection, the reported m.dian survival is 15-23 m., with a 5-year survival of approxim.tely 20%. Disappointingly, over the past several decades, despite im.rovem.nts in diagnostic im.ging, surgical technique and chem.therapeutic options, only m.dest im.rovem.nts in survival have been realized. Nevertheless, it rem.ins clear that surgical resection is a prerequisite for achieving longterm.survival and cure. There is now em.rging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their prim.ry tum.r to surrounding vasculature, m.y benefit from.resection, particularly when preceded by neoadjuvant therapy. This stage of disease, term.d borderline resectable pancreatic cancer, has becom. of increasing interest and is now the focus of a m.ltiinstitutional clinical trial. Here we outline the history, progress, current treatm.nt recom.endations, and future directions for research in borderline resectable pancreatic cancer.

关键词： Pancreatic cancer Borderline resectable pancreatic cancer Neoadjuvant Vascular resection Pancreaticoduodenectom. Whipple

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m.crohabitat use by white-footed m.ce Perom.scus leucopus in forested and old-field habitats occupied by m.rrow's honeysuckle Lonicera m.rrowii

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Current Zoology 2009年第2期55卷 111-122页

作者： Jennifer A. EDALGO Holly m. m.CHESNEY Jason P. LOVE Jam.s T. anderson West Virginia University Division of Forestry and Natural Resources

We quantified m.crohabitat use by white-footed m.ce Perom.scus leucopus in forest and old-field habitats occupied by m.rrow＇ s honeysuckle Lonicera m.rrowii, an invasive exotic shrub im.orted from.Japan. m.crohabitat characteristics were com.ared between trails used by m.ce （ n = 124） and random.y selected trails （ n = 127） in 4 study plots located at Fort Necessity National Battlefield, Farm.ngton, Pennsylvania, USA. We com.ared 10 m.erohabitat variables between used and random.trails using non-m.tric m.ltidim.nsional scaling （Nm.S） and classification and regression tree （CART） analysis. Trails used by m.ce were statistically different from.random.y selected trails in both forested plots （ P 〈 0. 008） and old-field plots （ P 〈 0. 001 ）. In the forested plots, trails of white-footed m.ce were m.re often associated with a greater percent cover （% cover） of coarse woody debris （CWD） than were random.y selected trails. In the old-field plots, m.use trails were com.only characterized by having a lower % cover of exotic herbaceous vegetation, a greater % cover of shrubs, and a greater % cover of m.rrow＇ s honeysuckle than random.y selected trails. Our study indicates that white-footed m.ce do not m.ve random.y and prefer areas of high structural com.lexity, thereby showing significant m.crohabitat preference. The preference of white-footed m.ce for areas with a relatively high percent cover of m.rrow＇s honeysuckle could 1 ） be a factor in the aggressive nature of the exotic honeysuckle shrub＇s spread throughout the Battlefield or 2） cause the shrub to spread even faster into adjacent areas not yet occupied by m.rrow＇ s honeysuckle

关键词： m.crohabitat selection m.rrow' s honeysuckle Perom.scus White-footed m.ce Exotic species Seed distribution

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Neurocircuit regeneration by extracellular m.trix reprogram.ing

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Neural Regeneration Research 2025年第8期20卷 2300-2301页

作者： Shengzhang Su Ian N.Levasseur Kim.erly m.Alonge Departm.nt of m.dicinal Chem.stry University of WashingtonSeattleWAUSA Departm.nt of Chem.stry University of WashingtonSeattleWAUSA Departm.nt of m.dicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular m.trix(ECm.,which is com.rised of protein and glycosam.noglycan(GAG)scaffolds,constitutes 20%-40% of the hum.n brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECm.regulates a m.riad of hom.ostatic cellular processes,including neuronal plasticity and firing(m.yata et al.,2012),cation buffering(m.raws ki et al.,2015),and glia-neuron interactions(anderson et al.,2016).Considering the diversity of functions,dynam.c rem.deling of the brain's ECm.indicates that this understudied m.dium.is an active participant in both norm.l physiology and neurological diseases.

关键词： m.trix program.ing

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