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Inhibition of Neuroblastoma Cell Growth by Difluoromethylornithine (DFMO) and Bortezomib through Suppression of LIN28 and MYCN

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Journal of Cancer Therapy 2017年第6期8卷 561-578页

作者： Maria E. Rich Ping Zhao Abhinav B. Nagulapally jeffrey bond Giselle L. Saulnier Sholler Pediatric Oncology Research Program Helen DeVos Children’s Hospital Grand Rapids MI USA College of Human Medicine Michigan State University Grand Rapids MI USA

Neuroblastoma (NB) is the most common childhood cancer arising from the nervous system. Many high-risk neuroblastoma (HRNB) patients develop relapse after initial response to induction treatment and overall long term survival remains poor (less than 60%), emphasizing the need for new therapeutic approaches and more effective treatments. Combination therapies present a favorable approach to improve efficacy, decrease toxicity, and reduce development of drug resistance. Difluoromethylornithine (DFMO) has shown promise in recent clinical trials as a therapeutic agent in treating HRNB. Proteasomes are known to play an important role in tumor cell growth. Bortezomib was the first proteasome inhibitor shown to have anticancer activity clinically. In this study we explore the mechanistic and therapeutic effects of the novel drug combination of DFMO and bortezomib in NB. Cell proliferation studies demonstrated synergistic inhibition of NB cell growth. Bortezomib induced cleaved caspase-3 apoptotic pathway whereas DFMO induced a cytostatic effect on NB cells. Western blot analyses demonstrated down regulation of MYCN, LIN28 and NF-kB in response to DFMO and bortezomib, pathways that are important in cancer stem cells. A decrease in ATP-per-cell when treated with combination therapy suggests inhibition of glycolytic metabolism in NB cells. DFMO as a single agent or in combination with bortezomib significantly reduced tumor growth in xenograft mice. Given the lack of effective treatments, DFMO coupled with bortezomib offers a potential new therapeutic treatment for children with NB.

关键词： Neuroblastoma DFMO Bortezomib LIN28B Glycolytic Metabolism

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Coupled Inversion of Pressure and Tiltmeter Data for Mapping Hydraulic Fracture Geometry

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Acta Mechanica Solida Sinica 2024年第3期37卷 396-405页

作者： Zuorong Chen Xiaofang Jiang Zhejun Pan Robert G.jeffrey National Key Laboratory of Continental Shale Oil Northeast Petroleum UniversityDaqing163318China SCT Operation Pty.Ltd. PO Box 824WollongongNSW2520Australia

Pressure and tilt data are jointly inverted to simultaneously map the orientation and dimensions of a hydraulic *** deformation induced by a fracture under internal pressure is modeled using the distributed dislocation *** planar fracture is represented by four quarter ellipses,joined at the center and sharing *** configuration provides a straightforward model for characterizing asymmetric fracture *** inverse problem of mapping the fracture geometry is formulated using the Bayesian probabilistic method,combining the a priori information on the fracture model with updated information from pressure and tilt *** the nonlinear inverse problem is achieved by pseudo-randomly sampling the posterior probability distribution through the Markov chain Monte Carlo *** resulting posterior probability distribution is then explored to assess uncertainty,resolution,and correlation between model *** experiments are conducted to verify the accuracy and validity of the proposed analysis method in mapping the fracture geometry using synthetic pressure and tilt data.

关键词： Hydraulic fracture mapping Coupled inversion Tilt Treating pressure

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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： jeffrey A Lowell Michael J Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

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Nano-enhanced solid-state hydrogen storage:Balancing discovery and pragmatism for future energy solutions

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Nano Research 2024年第10期17卷 8729-8753页

作者： Chaochao Dun Xinyi Wang Linfeng Chen Sichi Li Hanna M.Breunig jeffrey J.Urban The Molecular Foundry Lawrence Berkeley National Laboratory BerkeleyBerkeleyCA 94720USA Energy Analysis and Environmental Impacts Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Lawrence Livermore National Laboratory LivermoreCA 94550USA

Nanomaterials have revolutionized the battery industry by enhancing energy storage capacities and charging speeds,and their application in hydrogen(H_(2))storage likewise holds strong potential,though with distinct challenges and mechanisms.H_(2) is a crucial future zero-carbon energy vector given its high gravimetric energy density,which far exceeds that of liquid ***,its low volumetric energy density in gaseous form currently requires storage under high pressure or at low *** review critically examines the current and prospective landscapes of solid-state H_(2) storage technologies,with a focus on pragmatic integration of advanced materials such as metal-organic frameworks(MOFs),magnesium-based hybrids,and novel sorbents into future energy *** materials,enhanced by nanotechnology,could significantly improve the efficiency and capacity of H_(2) storage systems by optimizing H_(2) adsorption at the nanoscale and improving the kinetics of H_(2) uptake and *** discuss various H_(2) storage mechanisms—physisorption,chemisorption,and the Kubas interaction—analyzing their impact on the energy efficiency and scalability of storage *** review also addresses the potential of“smart MOFs”,single-atom catalyst-doped metal hydrides,MXenes and entropy-driven alloys to enhance the performance and broaden the application range of H_(2) storage systems,stressing the need for innovative materials and system integration to satisfy future energy ***-throughput screening,combined with machine learning algorithms,is noted as a promising approach to identify patterns and predict the behavior of novel materials under various conditions,significantly reducing the time and cost associated with experimental *** closing,we discuss the increasing involvement of various companies in solid-state H_(2) storage,particularly in prototype vehicles,from a techno-economic *** forward-looking perspective underscores t

关键词： nanomaterials nanotechnology solid-state H_(2)storage techno-economic analysis model-driven material development processes

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New insights on the high-corrosion resistance of UHP Mg-Ge alloys tested in a simulated physiological environment

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Journal of Magnesium and Alloys 2024年第3期12卷 1026-1044页

作者： Ting Liu Xingrui Chen jeffrey Venezuela Yuan Wang Zhiming Shi Wenyi Chen Matthew Dargusch Centre for Advanced Materials Processing and Manufacturing(AMPAM) School of Mechanical and Mining Engineeringthe University of QueenslandBrisbaneQLD 4072Australia CSIRO Mineral Resources 1 Technology CourtPullenvaleQLD 4069Australia

UHP Mg-Ge alloys was recently found to provide excellent corrosion *** paper provides new insights on the mechanism of improved corrosion resistance of UHP Mg-Ge alloys in Hanks’*** studied UHP Mg-0.5Ge and UHP Mg-1Ge alloys showed superior corrosion resistance compared to UHP Mg and WE43,with the Mg-1Ge exhibiting the best corrosion *** exceptional corrosion resistance of the UHP alloy is attributed to(i)Mg_(2)Ge’s ability to suppress cathodic kinetics,(ii)Ge’s capability to accelerate the formation of a highly passive layer,and the(iii)low amounts of corrosion-accelerating impurities.

关键词： UHP Mg-Ge alloy Cathodic kinetics suppression Biodegradable metals In vitro corrosion Magnesium corrosion.

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Three cases of uncommon medication-associated osteonecrosis of temporal bone

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世界耳鼻咽喉头颈外科杂志英文版 2024年第03期10卷 237-240页

作者： VanDolah Hunter Crossley Jason R. jeffrey Kim H. Georgetown University School of Medicine Washington DC USA Department of Otolaryngology–Head and Neck Surgery MedStar Georgetown University Hospital Washington DC USA

Introduction: Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic agents. Here, we present the first case of tyrosine-kinase inhibitor-related external auditory canal (EAC) osteonecrosis as well as two cases related to anti-resorptive ***: A retrospective case ***: Case one: an 84-year-old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally. She had a history of osteoporosis treated with denosumab and risedronic acid. She successfully underwent left EAC reconstruction using an inferiorly-based pedicle periosteal flap while the right ear canal was managed conservatively. Case two: a 69-year-old male presented with osteonecrosis of the right EAC. He had a history of osteoporosis treated with alendronic acid and zoledronic acid. His osteonecrosis is conservatively managed with local debridement and antibiotic application. Case three: a 60-year-old male presented with osteonecrosis of the right inferior EAC. He had a history of chronic myelogenous leukemia treated with a tyrosine-kinase inhibitor, imatinib. After failing conservative therapy, he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his ***: Anti-resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis. When a local debridement and antibiotic therapy fail, definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

关键词： bisphosphonates denosumab external auditory canal imatinib medication-related osteonecrosis osteonecrosis temporal bone tyrosine-kinase Inhibitors

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A Pilot Trial Testing the Feasibility of Using Molecular-Guided Therapy in Patients with Recurrent Neuroblastoma

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Journal of Cancer Therapy 2012年第5期3卷 602-612页

作者： Giselle L. Saulnier Sholler William Ferguson Genevieve Bergendahl Erika Currier Shannon R. Lenox jeffrey bond Marni Slavik William Roberts Deanna Mitchell Don Eslin Jacqueline Kraveka Joel Kaplan Nehal Parikh Suman Malempati Gina Hanna Emily Eugster David Cherba Jeremy Miller Craig Webb Cardinal Glennon Children’s Hospital Saint Louis University School of Medicine St. Louis University St. Louis USA Center for Cancer Genomics and Computational Biology Pediatric Oncology Translational Research Program at the Van Andel Research Institute in Grand Rapids Grand Rapids USA Center for Children’s Cancer and Blood Disorders Arnold Palmer Hospital for Children MD Anderson Cancer Center Orlando Orlando USA Department of Pediatric Oncology Helen DeVos Children’s Hospital Michigan State University Grand Rapids USA Department of Pediatric Oncology Oregon Health Science University Portland USA Division of Hematology/Oncology 2J Connecticut Children’s Medical Center Hartford USA Pediatric Hematology/Oncology Medical University of South Carolina Charleston USA Pediatric Oncology Levine Children’s Hospital Charlotte USA Rady Children’s Hospital San Diego University of California San Diego School of Medicine at the University of California San Diego San Diego USA Vermont Cancer Center Department of Medicine University of Vermont Burlington USA

Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of neuroblastoma with existing therapeutic agents may result in a rational, data-driven approach with potential to improve clinical outcomes. Methods: The primary objective of this pilot study was to evaluate the feasibility of supporting real-time treatment decisions through predictive modeling of genome-wide mRNA gene expression data from neuroblastoma tumor biopsies. Feasibility was defined as completion of tumor biopsy, histopathological evaluation, RNA extraction and quality control, gene expression profiling within a CLIA-certified laboratory, bioinformatic analysis, generation of a drug predicttion report, molecular tumor board review yielding a formulated treatment plan, and independent medical monitor review within a 2-week period. Results: Five patients with multiply relapsed or refractory neuroblastoma were enrolled between April and June 2010. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-7 days), reports which linked this data into medically actionable drug candidates (1-5 days), molecular tumor board (1-3 days) and independent medical monitor review (1 day) were all completed in real-time. The average time was 10.5 days for all patients. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in less than 12 days. This warrants further testing in a Phase I study to determine safety of predicted treatments and evaluate whether the information obtained in these analyses would result in patient benefit.

关键词： Neuroblastoma Molecular Guided Therapy Predictive Therapies Molecular Profiling Genomic Profiling Pediatric Cancer

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Advances in ground heat exchangers for space heating and cooling:Review and perspectives

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Energy and Built Environment 2024年第2期5卷 255-269页

作者： Ping Cui Weibo Yang Wenke Zhang Ke Zhu jeffrey D.Spitler Mingzhi Yu School of Thermal Engineering Shandong Jianzhu UniversityJinanShandong 250101China College of Electrical Energy and Power EngineeringYangzhou UniversityYangzhouJiangsu 225127China Department of Mechanical Engineering Oklahoma State UniversityStillwaterOKUSA

As a renewable energy source,geothermal energy has been widely used to provide space heating and cooling for *** thermal performance of ground heat exchanger(GHE)is significant for the operating efficiency of the ground source heat pump(GSHP)*** paper presents a comprehensive review of developments and advances of three kinds of GHE,including vertical borehole GHE(VBGHE),Pile GHE(PGHE),and deep borehole GHE(DBGHE)which are currently popular in larger GSHP ***,analytical models proposed to ana-lyze heat transfer process of VBGHE with different geological conditions are summarized,such as homogenous or heterogeneous ground,with or without groundwater *** and short-time step models and measures to improve GHE thermal performance are also ***,a summary of research advances in PGHE is provided,which includes the heat transfer models of PGHE,the effects of geometric structure,oper-ation modes,pile spacing,use of phase change material(PCM),thermal properties of PCM,thermo-mechanical behavior and/or thermal performance of *** effects of groundwater flow direction and velocity on PGHE are also summarized in ***,models of three kinds of DBGHEs,i.e.,deep coaxial GHE(DCGHE),deep U-bend GHE(DUGHE)and super-long gravity heat pipe(SLGHP),are *** physical bases of the dif-ferent analytical models are elaborated and also their advantages and disadvantages are *** in numerical modelling and improving numerical model calculation speed of DCBHE,DCBHE array,and DUBHE are *** review provides a meaningful reference for the further study of GHEs.

关键词： Vertical borehole ground heat exchanger Pile ground heat exchanger Deep borehole ground heat exchanger Modelling

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In vivo measurement of NADH fluorescence lifetime in skeletal muscle via -ber-coupled time-correlated single photon counting

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 121-134页

作者： Kathryn M.Priest Jacob V.Schluns Nathania Nischal Colton L.Gattis jeffrey C.Wolchok Timothy J.Muldoon Department of Biomedical Engineering University of Arkansas FayettevilleARUSA

Nicotinamide adenine dinucleotide(NADH)is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis,the tricarboxylic acid cycle,and oxidative phosphorylation(OXPHOS).NADH is autofluorescent,and itsfluorescence lifetime can be used to infer metabolic dynamics in living ***-coupled time-correlated single photon counting(TCSPC)equipped with an implantable needle probe can be used to measure NADH lifetime in vivo,enabling investigation of changing metabolic demand during muscle contraction or tissue *** study illustrates a proof of concept for point-based,minimally-invasive NADHfluorescence lifetime measurement in *** muscle loss(VML)injuries were created in the left tibialis anterior(TA)muscle of male Sprague Dawley *** lifetime measurements were collected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscles,which was subsequently-t to a biexponential decay model to yield a metric of NADH utilization(cytoplasmic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest,suggesting higher levels of free NADH in contracting and recovering muscle,indicating increased rates of *** injured muscle,this ratio was higher than uninjured muscle overall but decreased over time,which is consistent with current knowledge of inflammatory response to injury,suggesting tissue regeneration has *** data suggest that-ber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation.

关键词： Glycolysis oxidative phosphorylation energy metabolism volumetric muscle loss

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Supplementation of vitamin E or a botanical extract as antioxidants to improve growth performance and health of growing pigs housed under thermoneutral or heat-stressed conditions

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1101-1118页

作者： Ysenia V.Silva‑Guillen Consuelo Arellano jeffrey Wiegert R.Dean Boyd Gabriela E.Martinez Eric van Heugten Department of Animal Science North Carolina State UniversityRaleighNC 27695USA Department of Statistics North Carolina State UniversityRaleighNC 27695USA Department of Animal Science Texas A&M UniversityCollege StationTX 77843USA Animal Nutrition Research LLCAlvatonKY 42122USA.

Background Heat stress has severe negative consequences on performance and health of pigs,leading to significant economic *** objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance,intestinal health,and oxidative and immune status in grow-ing pigs housed under heat stress *** Duplicate experiments were conducted,each using 64 crossbred pigs with an initial body weight of 50.7±3.8 and 43.9±3.6 kg and age of 13-week and 12-week,***(n=128)were housed individually and assigned within weight blocks and sex to a 2×4 factorial arrangement consisting of 2 environments(thermo-neutral(21.2℃)or heat-stressed(30.9℃))and 4 supplementation treatments(control diet;control+100 IU/L of D-α-tocopherol in water;control+200 IU/kg of DL-α-tocopheryl-acetate in feed;or control+400 mg/kg of a botanical extract in feed).Results Heat stress for 28 d reduced(P≤0.001)final body weight,average daily gain,and average daily feed intake(-7.4 kg,-26.7%,and-25.4%,respectively)but no effects of supplementation were detected(P>0.05).Serum vitamin E increased(P<0.001)with vitamin E supplementation in water and in feed(1.64 vs.3.59 and 1.64 vs.3.24),but not for the botanical extract(1.64 vs.1.67 mg/kg)and was greater when supplemented in water ***(P=0.002).Liver vitamin E increased(P<0.001)with vitamin E supplementations in water(3.9 vs.31.8)and feed(3.9 vs.18.0),but not with the botanical extract(3.9 vs.4.9 mg/kg).Serum malondialdehyde was reduced with heat stress on d 2,but increased on d 28(interaction,P<0.001),and was greater(P<0.05)for antioxidant supplementation compared to *** proliferation was reduced(P=0.037)in the jejunum under heat stress,but increased in the ileum when vitamin E was supplemented in feed and water under heat stress(interaction,P=0.04).Tumor necrosis factor-αin jejunum and ileum mucosa decreased by heat stress(P<0.05)and was re

关键词： Botanical extract Growing pigs Heat stress Immune status Oxidative status Tocopherol Water

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