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Extracellular matrix remodelling in obesity and metabolic disorders

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Life Metabolism 2023年第4期2卷 7-21页

作者： Vish.l Musale david h.Wasserman Li Kang Division of Systems Medicine School of MedicineUniversity of DundeeDundee DD19SYUnited Kingdom Department of Molecular Ph.siology and Bioph.sics Mouse Metabolic Phenotyping CenterVanderbilt UniversityNashvilleTN 37235United States

Obesity causes extracellular matrix (ECM) remodelling wh.ch.can develop into serious path.logy and fibrosis, h.ving metabolic effects in insulin-sensitive tissues. Th. ECM components may be increased in response to overnutrition. Th.s review will focus on specific obesity-associated molecular and path.ph.siological mech.nisms of ECM remodelling and th. impact of specific interactions on tissue metabolism. In obesity, a complex network of signalling molecules such.as cytokines and growth.factors h.s been implicated in fibrosis. Increased ECM deposition contributes to th. path.genesis of insulin resistance at least in part th.ough.th. activation of cell surface integrin receptors and CD44 signalling cascades. Th.se cell surface receptors transmit signals to th. cell adh.some wh.ch.orch.strates an intracellular response th.t adapts to th. extracellular environment. Matrix proteins, glycoproteins, and polysacch.rides interact th.ough.ligand-specific cell surface receptors th.t interact with.th. cytosolic adh.sion proteins to elicit specific actions. Cell adh.sion proteins may h.ve catalytic activity or serve as scaffolds. Th. vast number of cell surface receptors and th. complexity of th. cell adh.some h.ve made study of th.ir roles ch.llenging in h.alth.and disease. Furth.r complicating th. role of ECM-cell receptor interactions is th. variation between cell types. Th.s review will focus on recent insigh.s gained from studies of two h.gh.y conserved, ubiquitous axes and h.w th.y contribute to insulin resistance and metabolic dysfunction in obesity. Th.se are th. collagen-integrin receptor-IPP (ILK-PINCh.Parvin) axis and th. h.aluronan-CD44 interaction. We speculate th.t targeting ECM components or th.ir receptor-mediated cell signalling may provide novel insigh.s into th. treatment of obesity-associated cardiometabolic complications.

关键词： extracellular matrix fibrosis insulin resistance obesity metabolism

A Lookah.ad Read Cach.： Improving Read Performance for Deduplication Backup Storage

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Journal of Computer Science & Tech.ology 2017年第1期32卷 26-40页

作者： Dongch.l Park Ziqi Fan Young Jin Nam david h. C. Du Department of Computer Science and Engineering University of Minnesota-Twin Cities Minneapolis MN 55455 U.S.A.

Data deduplication （dedupe for sh.rt） is a special data compression tech.ique. It h.s been widely adopted to save backup time as well as storage space, particularly in backup storage systems. Th.refore, most dedupe research.h.s primarily focused on improving dedupe write performance. h.wever, backup storage dedupe read performance is also a crucial problem for storage recovery. Th.s paper designs a new dedupe storage read cach. for backup applications th.t improves read performance by exploiting a special ch.racteristic： th. read sequence is th. same as th. write sequence. Consequently, for better cach. utilization, by looking ah.ad for future references with.n a moving window, it evicts victims from th. cach. h.ving th. smallest future access. Moreover~ to furth.r improve read cach. performance. it maintains a small log buffer to judiciously cach. future access data ch.nks. Extensive experiments with.real-world backup workloads demonstrate th.t th. proposed read cach. sch.me improves read performance by up to 64.3%

关键词： deduplication dedupe read cach. backup

Targeting th. PI3K-AKT-mTOR signaling network in cancer

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Ch.nese Journal of Cancer 2013年第5期32卷 253-265页

作者： Kh.rum h. Kh.n Timoth. A. Yap Li Yan david Cunningh.m GI and Lymph.ma Unit The Royal Marsden NHS Foundation Trust Drug Development Unit The Royal Marsden NHS Foundation Trust Merck & Co. Inc. US Ch.nese Anti-Cancer Association Sch.ol of Oncology Peking University Cancer Hospital Beijing Cancer h.spital

Th. ph.sph.inositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) path.ay is a frequently h.peractivated path.ay in cancer and is important for tumor cell growth.and survival. Th. development of targeted th.rapies against mTOR, a vital substrate along th.s path.ay, led to th. approval of allosteric inh.bitors, including everolimus and temsirolimus, for th. treatment of breast, renal, and pancreatic cancers. h.wever, th. suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel th.rapies against critical nodes of th.s path.ay are th.refore being actively investigated in th. clinic in multiple tumour types. In th.s review, we focus on th. progress of th.se agents in clinical development along with.th.ir biological rationale, th. need of predictive biomarkers and various combination strategies, wh.ch.will be useful in counteracting th. mech.nisms of resistance to th.s class of drugs.

关键词：信号网络癌症靶向治疗生物标志物磷酸肌醇细胞生长雷帕霉素哺乳动物

Stress enh.nces expression of calcium-binding proteins and NMDAR subunit genes in th. rat h.ppocampus

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Neuroprotection 2024年第2期2卷 167-178页

作者： Aravind Parth.sarath. Ramesh. h.numanth.ppa Sarojini R.Bulbule Kiran P.C. h.malath. Nanjaiah.Gopinath.G. Siddaiah.B.M. david Muniswamy Devaraju Kuramkote Sh.vanna Neuroch.mistry Lab Department of BiochemistryKarnatak UniversityDharwadIndia Department of Microbiology and Immunology University of Maryland School of MedicineBaltimoreMarylandUSA Department of Zoology Karnatak UniversityDharwadIndia

Backgrounds:Oxidative stress impairs th. function of calcium-binding proteins and deregulates calcium signaling in living *** h.ve previously explored th. overexpression of calcium-binding protein genes in a reactive oxygen and nitrogen species-induced in vitro cell model of stress th.t leads to ***,in in vivo models,low levels of stress leads to depressive-like ***,we aimed to analyze gene expression of major calcium-binding proteins(calcineurin,calmodulin,calsyntenin,synaptotagmin,and calreticulin)and N-meth.l-D-aspartic acid(NMDA)receptor subunits(glutamate receptor ionotropic[GluN]GluN1,GluN2A,and GluN2B)in th. h.ppocampus of stress-induced ***:Six-week-old male Wistar rats were assigned to two stress induction groups and a control group with.ut stress(n=6).Stress was induced by using h.(2)O_(2)(3%in water)or by immobilization(using a sticky mat)over a period of 30 *** of calcium-binding protein genes in th. h.ppocampus,antioxidant assays,structural alterations in h.ppocampal neurons,and depressive-like beh.vior were ***:Expression of genes encoding calcium-binding proteins calcineurin,calsyntenin,synaptotagmin and NMDA receptor subunit GluN1 was enh.nced in both.ch.mical and ph.sical stress-induced rats compared with.control rats(4.25±0.05 vs.1.03±0.02,ph. CA2 region of th. h.ppocampus were fewer and appeared disorganized compared with.control ***,stressinduced rats sh.wed decreased mobility and lower sucrose preference in beh.vioral studies compared with.control ***:Lower levels of reactive oxygen and nitrogen species(RONS)can also lead to stress in rats by affecting th.ir calcium signaling,buffering capacity in th. neurons leading to depressive symptoms.

关键词： calcineurin h.(2)O_(2) h.ppocampus immobilization NMDA receptors

Effectiveness of non-pyrimeth.mine-based regimens for toxoplasma enceph.litis:A systematic and meta-synth.sis study

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Asian Pacific Journal of Tropical Medicine 2022年第3期15卷 106-113页

作者： david Susanto Arth.r h.P.Mawuntu Finny Warouw Windy M.V.Wariki Neurology Department Faculty of MedicineSam Ratulangi University/R.D.Kandou HospitalManadoIndonesia Department of Community Medicine Faculty of MedicineSam Ratulangi UniversityManadoIndonesia

Objective:To examine th. differences in effectiveness and side effects between pyrimeth.mine-based and non-pyrimeth.mine-based regimens for toxoplasma enceph.litis since th. availability of pyrimeth.mine in Indonesia is currently limited due to its with.rawal from th. ***:A systematic review and meta-synth.sis study th.t was carried out by following a protocol guided by th. Preffered Reporting Items for Systematic Review and Meta-analysis(PRISMA).Effectiveness measures included clinical improvement,mortality,and radiological *** evaluated selected articles narratively because of th. limitations of *** risk of bias in RCTs was assessed using th. Coch.ane Risk of Bias tool for RCT(ROB 2.0)and coh.rt studies were assessed using th. Risk of Bias In Non-Randomized Studies of Interventions(ROBINS-1)*** quality was assessed using th. GradePro ***:We included two retrospective coh.rt studies and one *** outcome assessment in th.se th.ee studies did not sh.w significant difference in effectiveness between pyrimeth.mine-based and non-pyrimeth.mine-based regimens for toxoplasma enceph.litis ***,drug side effects were consistently h.gh.r in th. pyrimeth.mine-based ***:Th.s study h.s a h.gh.risk of *** quality of th. research.also h.s a low recommendation ***,th. results may be considered for application if a standard regimen is not available.

关键词： Toxoplasma enceph.litis Alternative treatment With.ut pyrimeth.mine Systematic review Meta-synth.sis

An El Nino Th.t“Failed to Appear”,an El Nino Th.t Was“h.ding”and a Prediction of th. Next El Nino

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Atmosph.ric and Climate Sciences 2018年第1期8卷 55-62页

作者： david h.lmes douglass Department of Ph.sics and Astronomy University of Roch.ster RochesterNew YorkUSA

Th.s paper discusses wh. model predictions of El Niño events fail. We begin by commenting on a recent retrospective about th. failed prediction of an El Niño during 1975 McPh.den et al. state th.t “for all th. advances in seasonal forecasting over th. past 40 years, th. fundamental problem of skillfully predicting th. development of ENSO events and th.ir consequences still ch.llenges th. scientific community.” In a second paper McPh.den, th.s time alone, discusses th. case of a “monster” El Niño “th.t failed to materialize in 2014”. Unbeknown to McPh.den, th.se two climate “nonevents” h.ve already been discussed and “explained” in some details in papers th.t report th.t th. climate system consists of a series of finite time segments bounded by abrupt climate sh.fts. Th.se finite time segments are ph.se-locked to th. 2nd or 3rd subh.rmonic of an annual forcing. Th.s paper will be an updated review of th.se “explanations”. Additionally, we note th.t th. climate system is presently (August 2017) in a ph.se-locked state of period 3 years th.t began in 2009 to make a qualified prediction: Th. next El Niño will occur during boreal winter of 2018 unless th.s ph.se-locked state terminates before th.n.

关键词： El Nino ENSO Climate Ph.se-Locked States Climate Sh.fts

Observation of Ph.se-Locked States in th. Atlantic Multi-Decadal Oscillation(AMO)

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Atmosph.ric and Climate Sciences 2018年第3期8卷 344-354页

作者： david h.lmes douglass Department of Ph.sics and Astronomy University of RochesterRochesterNYUSA

We report th.t th. Atlantic Multi-Decadal Oscillation (AMO) sh.ws th. same ph.se-locked states of period 2 and 3 years th.t h.ve been reported in many oth.r climate indices. In addition, we find th.t th. report by Muller, Curry et al. of an oscillation in th. AMO of 9.1 years is a misinterpretation of a maximum in th. Fourier spectrum.

关键词： Climate Sh.ft El Nino AMO Ph.se-Locked States

h.patocellular carcinoma national burden across different geograph.cal regions in th. United States between 2001 and 2020

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World Journal of Meth.dology 2024年第4期14卷 110-120页

作者： Yazan Abboud Raj Malh.tra Muh.mmad h.ssaan Arif Maan Anna Math.w Ibrah.m Abboud Ch.n-Wei Pan Saqr Alsakarneh.Fouad Jaber Islam Moh.med david Kim Nikolaos T Pyrsopoulos Department of Internal Medicine Rutgers New Jersey Medical SchoolNewarkNJ 07103United States University of California Riverside Sch.ol of Medicine RiversideCA 92521United States Department of Internal Medicine John H Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine University of Missouri-Kansas CityKansasMO 64108United States Division of Gastroenterology and h.patology Rutgers New Jersey Medical SchoolNewarkNJ 07101United States

BACKGROUND Wh.le prior data sh.wed an increasing incidence of h.patocellular carcinoma(h.C)in th. United States,th.re are limited compreh.nsive and comparative data on th. geograph.cal variations of h.C trends in different demograph.cspecific *** To evaluate sex and age-specific incidence rates and time trends in different geograph.cal regions in th. United *** Age-adjusted h.C incidence rates were collected from th. United States Cancer Statistics(USCS)database wh.ch.covers approximately 98%of th. population in th. United *** rates were stratified by sex,age,and geograph.cal *** percentage ch.nge(APC)and average APC(AAPC)were estimated using Joinpoint Regression.A pairwise comparison was conducted between sex-specific *** Th.re were 467344 patients diagnosed with.h.C in th. United States in th. USCS database between 2001 and *** rates and trends varied by geograph.cal *** looking at th. West region(115336 patients),incidence rates of h.C were overall increasing and also increasing in older ***,wh.n evaluating younger adults,h.C incidence rates decreased in men but not in women with.a sex-specific absolute AAPC-difference of 2.15(P=0.005).Wh.n evaluating th. Midwest region(84612 patients),similar results were *** incidence rates were increasing in th. overall population and in older adults as well,th.y were decreasing in younger men but not in women with.a sex-specific absolute AAPC-difference of 1.61(Ph. North.ast region(87259 patients),th. analysis sh.wed similar results with.decreasing h.C incidence rates in younger men but not counterpart women(Sex-specific AAPC-difference=3.26,Ph.n evaluating th. south.180137 patients),th. results were also decreasing in younger men but not in women(Sex-specific AAPC-difference=2.55,Ph. United States population sh.ws an increasing incidence of h.C across all

关键词： h.patocellular carcinoma Incidence Epidemiology h.alth.disparity Geograph.

Th. ALMaQUEST Survey ⅩⅤ: Th. dependence of th. molecular-to-atomic gas ratios on resolved optical diagnostics

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Science Ch.na(Ph.sics,Mech.nics & Astronomy) 2024年第9期Mechanics & Astronomy) .卷 178-200页

作者： Niankun Yu Zh.ng Zh.ng Ch.o-Wei Tsai Pei Zuo Sara L.Ellison david V.Stark Di Li Jingwen Wu Karen L.Masters Ting Xiao Yingh.i Zh.ng Zongnan Li Kai Zh.ng h.ngying Ch.n Sh. Liu Sih.n Jiao Fanyi Meng National Astronomical Observatories Chinese Academy of Sciences Key Laboratory of Radio Astronomy and Tech.ology Chinese Academy of Sciences Institute for Frontiers in Astronomy and Astroph.sics Beijing Normal University Sch.ol of Astronomy and Space Science University of Chinese Academy of Sciences Department of Ph.sics & Astronomy University of Victoria Departments of Ph.sics and Astronomy Haverford College Space Telescope Science Institute Zh.jiang Laboratory New Cornerstone Science Laboratory Sch.ol of Ph.sics Zhejiang University

Th. atomic-to-molecular gas conversion is a critical step in th. baryon cycle of galaxies,wh.ch.sets th. initial conditions for subsequent star formation and influences th. multi-ph.se interstellar *** compiled a sample of 94 nearby galaxies with.observations of multi-ph.se gas contents by utilizing public h.,CO,and optical IFU data from th. Ma NGA survey togeth.r with.new FAST h.*** agreement with.previous results,our sample sh.ws th.t th. global molecular-to-atomic gas ratio(Rmol≡log Mh./Mh.) is correlated with.th. global stellar mass surface density μ*with.a Kendall's τ coefficient of 0.25 and ph.ly but still correlated with.stellar mass and NUV-r color,and not related to th. specific star formation rate（sSFR）.Th. cold gas distribution and kinematics inferred from th. h.and CO global profile asymmetry and sh.pe do not significantly rely on *** to th. availability of kpc-scale observations of MaNGA,we decompose galaxies into h.,composite,and AGN-dominated regions by using th. BPT *** increasing Rmol,th. fraction of h.regions with.n 1.5 effective radius decreases sligh.ly;th. density distribution in th. spatially resolved BPT diagram also ch.nges significantly,suggesting ch.nges in metallicity and ionization *** with.h.gh.Rmoltend to h.ve h.gh.oxygen abundance,both.at one effective radius with.a Kendall's τ coefficient of 0.37(ph.ir central *** all parameters investigated h.re,th. oxygen abundance at one effective radius h.s th. strongest relation with.global *** dependence of gas conversion on gas distribution and galaxy ionization states is *** contrast,th. observed positive relation between oxygen abundance（μ*） and Rmolindicates th.t th. gas conversion is efficient in regions of h.gh.metallicity（density）.

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