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Measurement of oxygen consumption rates of human renal proximal tubule cells in an array of organ-on-chip devices to monitor drug-induced metabolic shifts

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Microsystems & Nanoengineering 2022年第5期8卷 149-160页

作者： Samuel H.Kann Erin M.Shaughnessey Jonathan R.Coppeta Hesham Azizgolshani Brett CIsenberg Else M.Vedula Xin Zhang joseph l.charest Draper Scholar 555 Technology SquareCambridgeMA 02139USA Department of Mechanical Engineering Boston University110 Cummington MallBostonMA 02215USA Department of Biomedical Engineering Tufts University4 Colby StreetMedfordMA 02155USA Draper 555 Technology SquareCambridgeMA 02139USA Present address:Biogen 225 Binney StreetCambridgeMA 02142USA

Measurement of cell metabolism in moderate-throughput to high-throughput organ-on-chip(OOC)systems would expand the range of data collected for studying drug effects or disease in physiologically relevant tissue ***,current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints,require labels or added substrates,and lack real-time ***,we integrated optical-based oxygen sensors in a high-throughput OOC platform and developed an approach for monitoring cell metabolic activity in an array of membrane bilayer *** membrane bilayer device supported a culture of human renal proximal tubule epithelial cells on a porous membrane suspended between two microchannels and exposed to controlled,unidirectional perfusion and physiologically relevant shear stress for several *** the first time,we measured changes in oxygen in a membrane bilayer format and used a finite element analysis model to estimate cell oxygen consumption rates(OCRs),allowing comparison with OCRs from other cell culture ***,we demonstrated label-free detection of metabolic shifts in human renal proximal tubule cells following exposure to FCCP,a drug known for increasing cell oxygen consumption,as well as oligomycin and antimycin A,drugs known for decreasing cell oxygen *** capability to measure cell OCRs and detect metabolic shifts in an array of membrane bilayer devices contained within an industry standard microtiter plate format will be valuable for analyzing flowresponsive and physiologically complex tissues during drug development and disease research.

关键词： metabolism culture OCR

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Disparate outcomes in Hispanic patients with metabolic dysfunctionassociated steatotic liver disease/steatohepatitis and type 2 diabetes: large cohort study

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World Journal of Diabetes 2024年第5期15卷 886-897页

作者： joseph Matthew Gosnell George Golovko Esteban Arroyave Akshata Moghe Michael l Kueht Omar AbdulSaldarriaga Kevin H McKinney Heather l Stevenson Monique R Ferguson Department of Pathology University of Texas Medical BranchGalvestonTX 77555United States Department of Pharmacology&Toxicology University of Texas Medical BranchGalvestonTX 77555United States Department of Medicine University of Texas Health Science Center at HoustonHoustonTX 77030United States Department of Surgery University of Texas Medical BranchGalvestonTX 77555United States Center for Tropical Diseases Department of Internal MedicineUniversity of Texas Medical BranchGalvestonTX 77555United States Department of Internal Medicine University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASlD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient ***,these conditions seem to have disparate rates and outcomes between different ethnic *** combination of MASlD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South *** To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic *** This cohort analysis was conducted with data obtained from TriNetX,llC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations *** cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast *** This study findings revealed Hispanics/latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/latino *** mortality in Hispanics/latinos was lower within the United States group and not statistically elevated in the UTMB *** This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.

关键词： Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Hispanic Diabetes mellitus TriNetX Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Steatotic liver disease Hepatocellular carcinoma

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Serum ferritin and the risk of early-onset colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3496-3506页

作者： Adam l Urback Kylee Martens Hannah Stowe McMurry Emerson Y Chen Caitlin Citti Anil Sharma Adel Kardosh joseph J Shatzel Division of Internal Medicine Oregon Health&Science UniversityPortlandOR 97239United States Division of Hematology and Medical Oncology Knight Cancer InstituteOregon Health&Science UniversityPortlandOR 97239United States Division of Gastroenterology&Hepatology Oregon Health&Science UniversityPortlandOR 97239United States

BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced *** serum ferritin is often incidentally discovered in young adults,however,the indication for endoscopy in EO-CRC is *** To compare serum ferritin between patients with EO-CRC and healthy controls(HCs),and examine the association of serum ferritin in EO-CRC with patient-and disease-specific *** A retrospective study of patientsly-diagnosed EO-CRC was conducted from 1/2013-12/*** were included if serum ferritin was measured within 2 years prior to 1 year following CRC histologic *** supplement the analysis,a cohort of HCs meeting similar inclusion and exclusion criteria were identified for comparison.A sensitivity analysis including only patients with serum ferritin obtained at or before diagnosis was separately performed to minimize risk of *** Among 85 patients identified with EO-CRC(48 females),the median serum ferritin level was 26 ng/ml(rangel).Compared to HCs(n=80211),there were a higher proportion of individuals with EO-CRC with serum ferritinl(female 65%,male 40%)versus HCs(female 32.1%,male 7.2%)age 29-39 years(P=0.002 and Ply).Stage IV disease was associated with significantly higher serum ferritin compared to less advanced stages(Plower than levels obtained after *** findings were confirmed in the sensitivity *** Severe iron deficiency may indicate an increased risk of EO-CRC,particularly at earlier *** studies defining the optimal serum ferritin threshold and routine incorporation of serum ferritin in screening algorithms is essential to develop more effective screening strategies for EO-CRC.

关键词： Early-onset Young-onset Colorectal cancer Age Ferritin Iron deficiency

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Machine-learning-Assisted Design of Deep Eutectic Solvents Based on Uncovered Hydrogen Bond Patterns

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Engineering 2024年第8期39卷 74-83页

作者： Usman l.Abbas Yuxuan Zhang joseph Tapia Selim Md Jin Chen Jian Shi Qing Shao Department of Chemical and Materials Engineering University of KentuckyLexingtonKY 40506USA Department of Biosystems and Agricultural Engineering University of KentuckyLexingtonKY 40506USA Institute for Biomedical Informatics Department of Computer ScienceUniversity of KentuckyLexingtonKY 40506USA

Non-ionic deep eutectic solvents(DESs)are non-ionic designer solvents with various applications in catalysis,extraction,carbon capture,and ***,discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES *** search for DES relies heavily on intuition or trial-and-error processes,leading to low success rates or missed *** that hydrogen bonds(HBs)play a central role in DES formation,we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning(Ml)models to discover new DES *** first analyze the HB properties of 38 known DES and 111 known non-DES systems using their molecular dynamics(MD)simulation *** analysis reveals that DES systems have two unique features compared to non-DES systems:The DESs have①more imbalance between the numbers of the two intra-component HBs and②more and stronger inter-component *** on these results,we develop 30 Ml models using ten algorithms and three types of HB-based *** model performance is first benchmarked using the average and minimal receiver operating characteristic(ROC)-area under the curve(AUC)*** also analyze the importance of individual features in the models,and the results are consistent with the simulation-based statistical ***,we validate the models using the experimental data of 34 *** extra trees forest model outperforms the other models in the validation,with an ROC-AUC of *** work illustrates the importance of HBs in DES formation and shows the potential of Ml in discovering new DESs.

关键词： Machine learning Deep eutectic solvents Molecular dynamics simulations Hydrogen bond Molecular design

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Comparisons of oxbow lake fish assemblages in relation to bigheaded carp establishment in the lower White River, Arkansas

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Ecological Processes 2024年第1期13卷 188-205页

作者： Michael A.Eggleton Cody J.Salzmann joseph E.Kaiser Shannon C.F.Smith Department of Aquaculture and Fisheries University of Arkansas at Pine Bluff Arkansas Game and Fish Commission Virginia Institute of Marine Science

Background Since the late 1990s, bigheaded carps(largely silver carp [Hypophthalmichthys molitrix] but also bighead carp [H. nobilis]) have established throughout the lower Mississippi River basin. Using previously studied oxbow lakes in the lower White River basin, Arkansas, we compared current(2017, “post-carp” establishment) fish assemblages to historical(2002, “pre-carp” establishment) fish assemblages. Fish assemblages were comprehensively assessed using multiple gears, including boat electrofishing, mini-fyke nets, and experimental small-mesh gill *** T-tests suggested that fish assemblage indices of richness, diversity, evenness, and dominance were often greater(P lected by boat electrofishing and experimental gill nets. However, all indices were generally similar(P > 0.05) between the pre-carp and post-carp period with fish assemblages depicted using mini-fyke nets. Nonmetric multidimensional scaling analyses indicated that fish assemblages differed structurally between pre-carp and post-carp periods. Assemblage differences were linked to both small and large abundance changes for more than 20 species. Abundances of gizzard shad(Dorosoma cepedianum), emerald shiner(Notropis atherinoides), pugnose minnow(Opsopoeodus emiliae), crappies(Pomoxis spp.), bluegill(lepomis macrochirus), orangespotted sunfish(l. humilis), and yellow bass(Morone mississippiensis) declined between the pre-carp and postcarp periods. Conversely, abundances of weed shiner(N. texanus), pallid shiner(Hybopsis amnis), longear sunfish(l. megalotis), buffalofishes(Ictiobus spp.), and gars(lepisosteus spp.) generally increased during the same *** Although not possible to conclude assemblage shifts were entirely related to bigheaded carps due to the absence of an appropriate reference system where carps did not establish, the wide establishment of these carps is one of the most pervasive changes to have occurred in the lower White

关键词： Bigheaded carp Silver carp Aquatic nuisance species Fish assemblage Oxbow lake large river

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Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： joseph Rich Brian Cole Teng li Brandon lu Hanyu Fu Brittany N.Smith Jianping Xia Shujie Yang Ruoyu Zhong James l.Doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony Jun Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid ***,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based *** simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet *** successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler ***,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration ***,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

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High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FlOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke li Jiarong Wu Yingshi Ouyang Yoel Sadovsky luke P.lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(lation method called Flocculation via Orbital Acoustic Trapping(FlOAT).The FlOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid *** adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the *** demonstrate the ability of FlOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FlOAT reduces biofluid starting volume requirements by a factor of 100(from 20 ml to 200µl),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

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Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells

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World Journal of Stem Cells 2024年第5期16卷 551-559页

作者： Amani Yehya joseph Azar Mohamad Al-Fares Helene Boeuf Wassim Abou-Kheir Dana Zeineddine Ola Hadadeh Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Inserm BiotisU1026University BordeauxBordeaux F-33000France Rammal Rammal lab Physio-Toxicity Environmental TeamFaculty of SciencesLebanese UniversityNabatieh 0000Lebanon

BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage *** exhibit a unique combination of self-renewal potency,unlimited proliferation,and *** latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ *** regulatory networks guide ESCs,directing their self-renewal and lineage-specific ***,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic ***-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly *** To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCl-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,*** mESC-T2(wild-type),mESC-BCl-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac *** hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of *** size of the generated EBs was measured in each condition compared to the wild *** the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the *** the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and ***,troponin T protein expression was evaluated through immunofluorescence and western blot *** Our findings showed that the upregulation of Bcl-

关键词： Mouse embryonic stem cells Self-renewal Apoptosis Cardiac differentiation B-cell lymphoma 2 PIM-2 Metallothionein-1

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Semisynthetic Derivatives of Sissotrin Isolated from Trifolium baccarinii Chiov. (Fabaceae) and Evaluation of Their Antibacterial Activities

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Advances in Biological Chemistry 2024年第1期14卷 27-39页

作者： Donald léonel Feugap Tsamo Cyrille Ngoufack Tagousop Arnaud joseph Nguetse Dongmo laurence Voutquenne-Nazabadioko David Ngnokam Research Unit of Applied and Environmental Chemistry Department of Chemistry Faculty of Science University of Dschang Dschang Cameroon Department of Organic Chemistry Faculty of Science University of Yaoundé I Yaoundé Cameroon Department of Basic Scientific Studies University Institute of Technology University of Ngaoundéré Ngaoundéré Cameroon Groupe Isolement et Structure Institut de Chimie Moléculaire de Reims (ICMR) Reims France

Starting from sissotrin (1), a natural isoflavonoid isolated from Trifolium baccarinii (Fabaceae), one new semisynthetic derivative, 6-nitrobiochanin A (1b) and two known derivatives, 8-nitrobiochanin A (1a) and 2",3",4",6"-tetraacetylsissotrin (1c) have been obtained after performing nitration and acetylation reactions. Their structures were assigned after interpretation of their spectrometric (HR-ESI-MS) and spectroscopic (NMR 1D and 2D) data and by comparison with those reported in the literature. The substrate as well as the semisynthetic derivatives were evaluated for their antibacterial activities against six strains. The results reveal that they are inactive or weakly active on the strains tested with the exception of 8-nitrobiochanin A (1a) which showed moderate activity (MIC = 62.5 μg∙ml−1) on Staphylococcus aureus ATCC 43300.

关键词： Trifolium baccarinii Isoflavonoid Nitration Acetylation Antibacterial Activity

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Manipulation of photosensory and circadian signaling restricts phenotypic plasticity in response to changing environmental conditions in Arabidopsis

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Molecular Plant 2024年第9期17卷 1458-1471页

作者： Martin William Battle Scott Fraser Ewing Cathryn Dickson joseph Obaje Kristen N.Edgeworth Rebecca Bindbeutel Rea lAntoniou-Kourounioti Dmitri A.Nusinow Matthew Alan Jones Plant Science Group School of Molecular BiosciencesUniversity of GlasgowGlasgow G128QQUK Danforth Plant Science Center St.LouisMO 63132USA Department of Biological and Biomedical Sciences Washington University in St.LouisSt.LouisMO 63130USA Present address:School of Biological and Environmental Sciences Liverpool John Moores UniversityLiverpool L22QPUK

Plants exploit phenotypic plasticity to adapt their growth and development to prevailing environmental *** of light and temperature signals is aided by the circadian system,which provides a temporal *** plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale,intensive agricultural practices since economically important traits(including vegetative growth and flowering time)can vary widely depending on local environmental *** prevents accurate prediction of harvesting times and produces a variable *** this study,we sought to restrict phenotypic plasticity and circadian regulation by manipulating signaling systems that govern plants'responses to environmental *** modeling of plant growth and develop-ment predicted reduced plant responses to changing environments when circadian and light signaling pathways were *** tested this prediction by utilizing a constitutively active allele of the plant photoreceptor phytochrome B,along with disruption of the circadian systemvia mutation of *** found that these manipulations produced plants that are less responsive to light and temper-ature cues and thus fail to anticipate *** engineered plants have uniform vegetative growth and flowering time,demonstrating how phenotypic plasticity can be limited while maintaining plant *** has significant implications for future agriculture in both open fields and controlled environments.

关键词： circadian developmental plasticity phenotypic plasticity external coincidence light temperature

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