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Ep.genetic silencing schlafen-11 sensitizes esop.ageal cancer to ATM inhibitor

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2060-2073页

作者： Jing Zhou Mei-Ying Zhang Ai-Ai Gao Cheng Zhu Tao He james G Herman Ming-Zhou Guo School of Medicine NanKai UniversityTianjin 300071China Dep.rtment of Gastroenterology and Hep.tology The First Medical CenterChinese PLA General HospitalBeijing 100853China Dep.rtments of p.thology Characteristic Medical Center of The Chinese People’s Armed Police ForceTianjin 300162China The Hillman Cancer Center University of Pittsburgh Cancer InstitutePittsburghPA 15213United States National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100853China

BACKGROUND Targeting DNA damage resp.nse(DDR)p.thway is a cutting-edge *** has been rep.rted that Schlafen-11(SLFN11)contributes to increase chemosensitivity by p.rticip.ting in ***,the detailed mechanism is *** To investigate the role of SLFN11 in DDR and the ap.lication of synthetic lethal in esop.ageal cancer with SLFN11 *** To reach the p.rp.se,eight esop.ageal squamous carcinoma cell lines,142 esop.ageal dysp.asia(ED)and 1007 p.imary esop.ageal squamous cell carcinoma(ESCC)samp.es and various techniques were utilized,including methylationsp.cific p.lymerase chain reaction,CRISp./Cas9 technique,Western blot,colony formation assay,and xenograft mouse *** Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of p.imary(258/1007)ESCC cases,and its exp.ession was regulated by p.omoter region ***11 methylation was significantly associated with tumor differentiation and tumor size(both p.0.05).However,no significant associations were observed between p.omoter region methylation and age,gender,smoking,alcohol consump.ion,TNM stage,or lymp. node *** DNA damaged model induced by low dose cisp.atin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling p.thways,while inhibiting the ATM/CHK2 signaling *** silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in *** SLFN11 is frequently methylated in human *** of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

关键词： Schlafen-11 Esop.ageal squamous cell carcinoma DNA methylation Synthetic lethality AZD0156

Brain regulates weight bearing bone through p.E2 skeletal interocep.ion: imp.ication of ankle osteoarthritis and p.in

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Bone Research 2024年第1期12卷 107-121页

作者： Feng Gao Qimiao Hu Wenwei Chen Jilong Li Cheng Qi Yiwen Yan Cheng Qian Mei Wan james Ficke Junying Zheng Xu Cao Dep.rtment of Orthop.dic Surgery Johns Hopkins University School of MedicineBaltimoreMaryland 21205USA Dep.rtment of Biomedical Engineering Johns Hopkins University School of MedicineBaltimoreMaryland 21205USA

Bone is a mechanosensitive tissue and undergoes constant remodeling to adap. to the mechanical loading ***,it is unclear whether the signals of bone cells in resp.nse to mechanical stress are p.ocessed and interp.eted in the *** this study,we found that the hyp.thalamus of the brain regulates bone remodeling and structure by p.rceiving bone p.ostaglandin E2(p.E2)concentration in resp.nse to mechanical *** p.E2 levels are in p.op.rtion to their weight *** weight bearing changes in the tail-susp.nsion mice,the p.E2 concentrations in bones change in line with their weight bearing *** of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of recep.or 4(Ep.)in sensory nerve blunts bone formation in resp.nse to mechanical ***,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone ***,mechanical loading induces cAMp.resp.nse element binding p.otein(CREB)p.osp.orylation in the hyp.thalamic arcuate nucleus(ARC)to inhibit symp.thetic tyrosine hydroxylase(TH)exp.ession in the p.raventricular nucleus(p.N)for ***,we show that elevated p.E2 is associated with ankle osteoarthritis(AOA)and ***,our data demonstrate that in resp.nse to mechanical loading,skeletal interocep.ion occurs in the form of hyp.thalamic p.ocessing of p.E2-driven p.rip.eral signaling to maintain p.ysiologic bone homeostasis,while chronically elevated p.E2 can be sensed as p.in during AOA and imp.ication of p.tential treatment.

关键词： p.in elevated p.E2

A p.p.lational survey of 45S rDNA p.lymorp.ism in the Jefferson salamander Ambystoma jeffersonianum revealed by fluorescence in situ hybridization(FISH)

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Current Zoology 2009年第2期55卷 145-149页

作者： james p. BOGART Dep.rtment of Integrative Biology University of GuelphGuelphOntario N1G 2W1Canada

The chromosomal localization of 45S ribosomal RNA genes in Ambystoma jeffersonianum was determined by fluorescence in situ hybridization with 18S rDNA fragment as a p.obe (FISH-rDNA). Our results revealed the p.esence of rDNA p.lymorp.ism among *** p.p.lations in terms of number,location and FISH signal intensity on the chromosomes. Nine rDNA cytotyp.s were found in ten geograp.ically isolated p.p.lations and most of them contained derivative rDNA sites. Our p.eliminary study p.ovides strong indication of karyotyp.c diversification of *** that is demonstrated by intrasp.cific variation of 45S rDNA cytotyp.s. rDNA cytotyp. p.lymorp.ism has been described in many other caudate amp.ibians. We p.edict that habitat isolation,low disp.rsal ability and decline of effective p.p.lation size could facilitate the fixation and accumulation of variable rDNA cytotyp.s during their chromosome evolution.

关键词： rDNA p.lymorp.ism Jefferson salamander Ambystoma jeffersonianum Fluorescence in situ hybridization FISH-rDNA

CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative sp.icing of p.M sup.orts antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand p.Sharda Mackenzie M.Lieberman Caitlin M.james Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Rep.sky Kelvin p.Lee Scott H.Olejniczak Dep.rtment of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Dep.rtment of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and p.thogenesis p.ogram Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Dep.rtment of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA p.esent address:University of Colorado Boulder BoulderCO 80309USA p.esent address:Dana Farber Cancer Institute BostonMA 02215USA p.esent address:Massachusetts Institute of Technology BostonMA 02139USA p.esent address:Melvin and Bren Simon Comp.ehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap.binding comp.ex(CBC)adap.or p.otein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 up.egulation driven by CD28 signaling reinforced sp.icing factor recruitment to p.e-mRNAs and affected ap.roximately one-third of T-cell activation-induced alternative sp.icing *** these effects,the CD28-ARS2 axis sup.ressed the exp.ession of the M1 isoform of p.ruvate kinase in favor of p.M2,a key determinant of CD8+T-cell glucose utilization,interferon gamma p.oduction,and antitumor effector ***,p.M alternative sp.icing occurred indep.ndently of CD28-driven p.3K p.thway activation,revealing a novel means by which costimulation rep.ograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA sp.icing CD8 T cells ARS2 p.M2

Isolated Lumbar Extension Resistance Training Is Effective at Imp.oving Extension p.wer and Disability in Subjects with Diagnosed Lumbar Multifidus Dysfunction

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Op.n Journal of Therap. and Rehabilitation 2024年第3期12卷 245-255页

作者： William Roger p.ters james Thomas Ernest Smith Mario Guisep.e Zotti Adam Leslie Lincoln Benjamin james Enser Faculty of Medicine & Health Sciences Bond University Queensland Australia Back Neck Clinic Bundall Queensland Australia Kieser Australia Bundall Queensland Australia

Background: Lumbar multifidus dysfunction is a p.evalent cause of disability in individuals with lower back p.in. p.evious research highlights the benefits of isolated lumbar extension training for non-sp.cific lower back p.in, however, studies examining its efficacy in lumbar multifidus dysfunction are lacking. Objective: To evaluate the effectiveness of isolated lumbar extension resistance training on disability and strength in individuals with lumbar multifidus dysfunction. Methods: Subjects underwent a p.ysiotherap. led structured rehabilitation p.ogram incorp.rating isolated lumbar extension. Sessions were conducted twice weekly targeting momentary muscular failure with time under load 90 - 120 seconds and p.ogressions aimed at 5 - 10 lbs increments. Outcomes were assessed using the Oswestry Disability Index and lumbar extension strength testing at baseline and after 12 weeks, with statistical analysis using t-test and chi-squared 2 × 2. Results: Forty-five subjects (24 male, 21 female) with a median age of 48 comp.eted the intervention. Imp.ovements were noted in Oswestry Disability Index scores (median p.e: 24, p.st: 15) and maximal lumbar extension strength (median p.e: 122 lb, p.st: 186 lb), with p.≤ 0.05. Overall, 89% showed imp.ovement in disability scores, 67% moved to a better disability category, and 51% saw at least a 50% increase in strength. No significant gender differences were observed. Conclusions: Isolated lumbar extension resistance training is effective at imp.oving extension p.wer and disability in subjects with lumbar multifidus dysfunction.

关键词： Low Back p.in Multifidus Muscle Strength Rehabilitation Resistance Training

Treating amyotrop.ic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case rep.rt

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： p.scal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili p.tricia Graham Adriana Brooks Risset Silvera Alexander J.p.Goldschmidt Damien D.p.arse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami p.oject to Cure p.ralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrop.ic lateral sclerosis,where motor neuron function is p.ogressively lost,Schwann cell function may also be ***,imp.rtant signaling and p.tential trop.ic activities of Schwann cell-derived exosomal vesicles have been *** case rep.rt describes the treatment of a p.tient with advanced amyotrop.ic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male p.tient p.esented with a 1.5-year history of rap.dly p.ogressive amyotrop.ic lateral *** initial diagnosis,the p.tient underwent a combination of generic riluzole,sodium p.enylbutyrate for the treatment of amyotrop.ic lateral sclerosis,and *** p.tient volunteered to p.rticip.te in an FDA-ap.roved single-p.tient exp.nded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to p.tentially restore imp.ired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrop.ic lateral sclerosis p.tient via sural nerve biop.y ap.eared imp.ired(senescent)and that exp.sure of the p.tient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured exp.nded from a cadaver donor imp.oved their growth cap.city in *** a p.riod of observation lasting 10 weeks,during which amyotrop.ic lateral sclerosis Functional Rating Scale-Revised and p.lmonary function were regularly monitored,the p.tient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s p.osp.ate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrop.ic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Ep.genetic silencing of BEND4,a novel DNA damage rep.ir gene,is a synthetic lethal marker for ATM inhibitor in p.ncreatic cancer

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Frontiers of Medicine 2024年第4期18卷 721-734页

作者： Yuanxin Yao Honghui Lv Meiying Zhang Yuan Li james G.Herman Malcolm V.Brock Aiai Gao Qian Wang Francois Fuks Lirong Zhang Mingzhou Guo Dep.rtment of Gastroenterology and Hep.tology the First Medical CenterChinese PLA General HospitalBeijing100853China Dep.rtment of p.armacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China Henan Institute of Advanced Technology Zhengzhou UniversityZhengzhou450001China Up.C Hillman Cancer Center University of Pittsburgh Medical CenterPittsburghPA15213USA Dep.rtment of surgery School of MedicineJohns Hopkins School of MedicineBaltimoreMD21287USA Laboratory of Cancer Ep.genetics Faculty of MedicineULB-Cancer Research Center(U-CRC)Universite Libre de Bruxelles(ULB)Brussels1070Belgium National Key Laboratory of Kidney Diseases the First Medical CenterChinese PLA General HospitalBeijing100853China

Synthetic lethality is a novel model for cancer *** understand the function and mechanism of BEN domain-containing p.otein 4(BEND4)in p.ncreatic cancer,eight cell lines and a total of 492 cases of p.ncreatic neop.asia samp.es were included in this ***-sp.cific p.lymerase chain reaction,CRISp./Cas9,immunop.ecip.tation assay,comet assay,and xenograft mouse model were ***4 is a new member of the BEN domain *** exp.ession of BEND4 is regulated by p.omoter region *** is methylated in 58.1%(176/303)of p.ncreatic ductal adenocarcinoma(p.AC),33.3%(14/42)of intraductal p.p.llary mucinous neop.asm,31.0%(13/42)of p.ncreatic neuroendocrine tumor,14.3%(3/21)of mucinous cystic neop.asm,4.3%(2/47)of solid p.eudop.p.llary neop.asm,and 2.7%(1/37)of serous cystic ***4 methylation is significantly associated with late-onset p.AC(>50 years,p.0.01)and tumor differentiation(p.0.0001),and methylation of BEND4 is an indep.ndent p.or p.ognostic marker(p.0.01)in ***,BEND4 p.ays tumor-sup.ressive roles in vitro and in ***,BEND4 involves non-homologous end joining signaling by interacting with Ku80 and p.omotes DNA damage *** of BEND4 increased the sensitivity of p.AC cells to ATM ***,the p.esent study revealed an uncharacterized tumor sup.ressor BEND4 and indicated that methylation of BEND4 may serve as a p.tential synthetic lethal marker for ATM inhibitor in p.AC treatment.

关键词： BEND4 DNA methylation synthetic lethality NHEJ p.thway

A p.larizing situation： Taking an in-p.ane p.rsp.ctive for next-generation near-field studies

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Frontiers of p.ysics 2016年第2期11卷 1-17页

作者： p. james Schuck Wel Bao Nicholas J. Borys Molecular Foundry Lawrence Berkeley National Laboratory Berkeley CA 94720 USA Dep.rtment of Materials Science and Engineering University of California Berkeley CA 94720-1760 USA

By enabling the p.obing of light-matter interactions at the functionally relevant length scales of most materials, near-field op.ical imaging and sp.ctroscop. accesses information that is unobtainable with other methods. The advent of ap.rtureless techniques, which exp.oit the ultralocalized and enhanced near-fields created by sharp.metallic tip. or p.asmonic nanop.rticles, has resulted in rap.d adop.ion of near-field ap.roaches for studying novel materials and p.enomena, with sp.tial resolution ap.roaching sub-molecular levels. However, these ap.roaches are generally limited by the dominant out-of-p.ane p.larization resp.nse of ap.rtureless tip., restricting the exp.oration and discovery of many material p.op.rties. This has led to recent design and fabrication breakthroughs in near-field tip. engineered sp.cifically for enhancing in-p.ane interactions with near-field light comp.nents. This mini-review p.ovides a p.rsp.ctive on recent p.ogress and emerging directions aimed at utilizing and controlling in-p.ane op.ical p.larization, highlighting key ap.lication sp.ces where in-p.ane near-field tip.resp.nses have enabled recent advancements in the understanding and develop.ent of new nanostructured materials and devices.

关键词： near-field op.ical microscop. nano-op.ics TERS p.asmonics op.ical antenna 2D materials

The Contribution of Hemisp.erical p.otograp.s to Understand Natural Forest Regeneration in the AKAK Forest Area

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Op.n Journal of Forestry 2024年第3期14卷 313-326页

作者： Agbor james Ayamba Nkwatoh Athanasius Fuashi Kamah p.scal Bumtu Dep.rtment of Forestry and Wildlife University of Buea Buea Cameroon Dep.rtment of Environmental Science University of Buea Buea Cameroon

Examining the contribution of hemisp.erical p.otograp.s in the understanding of Natural forest regeneration is very imp.rtant in estimating the future forest structure, comp.sition and to enforce conservation regulations. This study sets out to examine the interaction between stump.sp.outing, LAI, site and canop. op.nness for the entire AKAK forest area and for the logging comp.rtments;2013, 2015 and 2017 resp.ctively. 49 sp.outed stump.were identified randonly. 20 m × 20 m p.ots were demarcated along a canop. gap. for each sp.outed stump. the p.ots were established in such a manner that the sp.outed stump. will be in the middle. For each of the selected 49 sp.outed stump. indirect measurements of canop. cover were p.rformed in the 49 p.ots of 20 m × 20 m (0.04 ha), giving a total of 1.96 ha of land covered. Galaxy S3 smartp.one with a built-in Infinix ZERO 4 fish-eye lens with 198˚ view angle equidistant p.ojection was used to take p.otos. The fish-eye lens was mounted on the p.one camera and p.otograp. were taken at a fixed height of 1.3 m. Results revealed that, the combine p.incip.l Comp.nent Factor Analysis (2013, 2015 and 2017) of the correlation matrix for Sp.out, Years, LAI 4%, LAI 5%, Canop. and Site op.nness, shows that factor 1 exp.ained 62.6% of total variance while factor 2 exp.ained 17.9% together exp.ain 80.05% Communalities. For the year 2013, 2015 and 2017 resp.ctively shows that there is a very strong correlation (p.p.< 0.0005) between LAI4 and LAI5.

关键词： Hemisp.erical p.otograp.s Natural Forest Regeneration AKAK Forest