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Do tensile and shear forces exerted on cells influence mechanotransduction through stored energy considerations?

BIOCELL 2024年第4期48卷 525-540页

作者： FREDERICK H.SILVER TANMAY DESHMUKH Department of Pathology and Laboratory Medicine Robert Wood Johnson Medical SchoolRutgersThe State University of New JerseyPiscatawayNJ 08854USA OptoVibronex LLC.Ben Franklin Tech PartnersBethlehemPA 18015USA

All tissues in the body are subjected externally to gravity and internally by collagenﬁbril and cellular retractive forces that create stress and energy equilibrium required for *** involves mechanical work(force through a distance)and energy storage as kinetic and potential *** leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue *** involves the application of energy directly to cells through integrin-mediated processes,cell-cell connections,stretching of the cell cytoplasm,and activation of the cell nucleus via yes-associated protein(YAP)and transcriptional coactivator with PDZ-motif(TAZ).These processes involve numerous complexes,intermediate molecules,and multiple *** pathways have been identiﬁed from research studies on vertebrate cell culture and from studies in *** pathways involve mechanosensors and other molecules that activate the *** review discusses the mitogen-activated protein kinase(MAPK)family,Hippo,Hedgehog,and Wingless-related integration site(WNT)/βcatenin signaling *** mediators covered includeβcatenin,ion channels,growth factors,hormone receptors,members of the Ras superfamily,and components of the linker of nucleoskeleton and cytoskeleton(LINC)***,the interrelationship among the different pathways remains to be clariﬁ***-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagenﬁbril *** energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin *** alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and *** coactivators then penetrate through the nuclear pores and inﬂuence nuclear cell *** in the balance of forces and energy applied to cells and tissues is hypothesized to shift th

关键词： MAPK family Hippo Hedgehog WNT pathway βcatenin Ion channels Growth factor receptors Hormone receptors Ras superfamily LINC complex Collagen Cadherins

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Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

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World Journal of Hepatology 2024年第7期16卷 1009-1017页

作者： Tung Huynh Delana MyAn Bui Tina Xiwen Zhou Ke-Qin Hu Department of Pharmacy University of California Irvine Medical CenterOrangeCA 92868United States university of Houston HoustonTX 77204United States Chicago Medical School at Rosalind franklin university North ChicagoIL 60064United States Division of Gastroenterology and Hepatology University of California IrvineSchool of MedicineOrangeCA 92868United States

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic *** To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with *** A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated *** The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,*** 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,*** baseline to switching week 144,the rates of ALT and AST60 mL/min was increased from 86.5%at baseline to 88.2%at switching week *** Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

关键词： Tenofovir alafenamide Tenofovir disoproxil fumarate Switching Hepatic fibrosis improvement Aspartate aminotransferase to platelet ratio index Fibrosis-4 Shear wave elastography

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Early calcium dysregulation in Alzheimer's disease:setting the stage for synaptic dysfunction

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Science China(Life Sciences) 2011年第8期54卷 752-762页

作者： Shreaya CHAKROBORTY Grace E.STUTZMANN Department of Neuroscience Rosalind Franklin University/the Chicago Medical School

Alzheimer's disease(AD) is an irreversible and progressive neurodegenerative disorder with no known cure or clear understanding of the mechanisms involved in the disease *** plaques,neurofibrillary tangles and neuronal loss,though characteristic of AD,are late stage markers whose impact on the most devastating aspect of AD,namely memory loss and cognitive deficits,are still *** studies demonstrate that structural and functional breakdown of synapses may be the underlying factor in AD-linked cognitive *** common element that presents with several features of AD is disrupted neuronal calcium *** intracellular calcium levels are functionally linked to presenilin mutations,ApoE4 expression,amyloid plaques,tau tangles and synaptic *** this review,we discuss the role of AD-linked calcium signaling alterations in neurons and how this may be linked to synaptic dysfunctions at both early and late stages of the disease.

关键词： calcium Alzheimer's neuron synaptic dysfunction plasticity ER ryanodine CICR

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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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Development and applications of the quasi‐dynamic triaxial apparatus for deep rocks

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Deep Underground Science and Engineering 2024年第1期3卷 70-90页

作者： Jinzhi Luo Yanyan Cai Jin Yu Jianzhi Zhang Yaoliang Zhu Yao Wei School of Civil Engineering Huaqiao UniversityXiamenFujianChina Zijin School of Geology and Mining Fuzhou UniversityFuzhouChina

The mechanical behaviors of deep rocks have always posed a challenge for the implementation and safe operation of major underground engineering *** this end,this study modified the existing mainstream rock mechanics instruments equipped with a dynamic disturbance loading system and developed a second‐generation TFD‐2000/D triaxial *** first‐generation device is equipped with an independent disturbance system and an advanced EDC‐580 all‐digital servo controller,which can apply disturbing load independently,implement the function of cyclic disturbance,and combine dynamic and static *** instrument was found to be reliable for use in analyzing the damage process of rocks in the disturbance test of *** second‐generation instrument tackles three limitations of the first‐generation instrument:(i)it upgrades the strain measurement system and uses extensometers with linear variable differential transformers to accurately measure deformation;(ii)it uses the self‐balanced chamber to replace the Hoek–franklin triaxial cell and auto‐balancing triaxial pressure chamber;and(iii)the loading rod is independently equipped with an EDC‐580 all‐digital servo controller,which measures precise *** experimental findings confirmed that the second‐generation instrument can be used for rock mechanics testing under cyclic disturbance loading,the disturbance–stress relaxation cycle,and the creep–fatigue *** this sense,the second‐generation instrument can be a useful addition to deep rock mechanical instruments and provide a valuable reference.

关键词： complex stress conditions deep rock disturbance loading modification of instrument rock mechanics

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Optimizing dietary lipid use to improve essential fatty acid status and reproductive performance of the modern lactating sow:a review

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Journal of Animal Science and Biotechnology 2016年第3期7卷 272-289页

作者： David S.Rosero R.Dean Boyd Jack Odle Eric van Heugten The Hanor Company FranklinKY 42134USA Department of Animal Science North Carolina State UniversityRaleighNC 27695USA

Dietary lipid supplementation benefits the prolific and high-producing modern lactating sow. A comprehensive review of recent studies showed that lipid supplementation increases average daily energy intake, which is partitioned for lactation as indicated by greater milk fat output and improved litter growth rate. Recent compelling findings showed that addition of particular lipids during lactation improved the subsequent reproductive outcome of sows. Such benefits were related to the level of dietary essential fatty acids（EFA, linoleic acid, C18：2n-6; and α-linolenic acid, C18：3n-3） during lactation. Lactation diets without supplemental EFA resulted in a pronounced negative balance（intake minus milk output） of linoleic（-25.49 g/d） and α-linolenic acid（-2.75 g/d）; which compromised sow fertility（farrowing rate 〈 75 % and culling rates 〉 25 % of weaned sows）. This phenomenon seems to be increasingly important with advancing sow age because of a progressive reduction of body EFA pool over successive lactations. The net effect of supplemental EFA during lactation was to create a positive EFA balance, which improved the subsequent reproduction of sows. Adequate linoleic acid intake improved the proportion of sows that farrowed in the subsequent cycle（Farrowing rate（%） = [（-1.5 × 10^-3× linoleic acid intake（g/d）^2）＋（0.53 × linoleic acid intake（g/d））＋（45.2）]; quadratic P = 0.002, R^2= 0.997, RMSE = 0.031）. In addition, increasing linoleic acid intake increased the number of pigs born in the subsequent cycle（total pigs born（n） = [（9.4 × 10^-5× linoleic acid intake（g/d）^2）＋（0.04 × linoleic acid intake（g/d））＋（10.94）]; quadratic P = 0.002, R^2= 0.997, RMSE = 0.031）. Supplemental α-linolenic acid resulted in a rapid return to estrus（sows bred： sows weaned = 94.2 %; wean-to-estrus interval = 4.0 d） and achieved a high retention of pregnancy（sows pregnant： sows bred = 98 %）. Collectively, we conclude that a minimum dietary intake of10 g/d of α-linolenic acid, simultaneous wit

关键词： Essential fatty acids Lactating sow Subsequent reproduction Supplemental lipids

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Patterns of climber distribution in temperate forests of the Americas

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Journal of Plant Ecology 2016年第6期9卷 724-733页

作者： Annik Schnitzler Javier Amigo Brack Hale Christophe Schnitzler Laboratoire Interdisciplinaire des Environnements Continentaux(LIEC) UMR 7360 Universitéde LorraineMetzFrance Laboratorio de Botánica Facultad de FarmaciaUniversidad de Santiago de CompostelaA CoruñaSpain franklin university switzerland SorengoSwitzerland Facultédes Sciences du Sport UnistraUniversitéde StrasbourgStrasbourgFrance

Aims and Methods We propose a standard protocol at the landscape to continental scale for examining to what extent the range of ecological conditions found in temperate latitudes explains the variations in climber species richness and *** protocol was tested in forests of the two *** data set included 151 climber *** selected four categorical traits and grouped these species into six clusters with regard to these *** records of American forests were first gathered into alliances,second combined with bioclimatic indices(rainfall,temperature,continentality).We obtained a total of 59 vegetational units in which we calculated values of climber species richness and proportion of *** units were ultimately gathered into five forest formations(characterized by leaf longevity).Wetlands and uplands were considered *** Findings Our results emphasize clear trends in large-scale patterns of climber distribution,independently of *** species richness(in particular woody climbers)peaks in moist and warm upland forests with oceanic climates,and where conifers are *** flooded areas,climber richness is also very high and peaks in seasonally flooded large *** ecological conditions of frost,dryness or lack of nutrients,climber species richness,abundance and trait diversity decline,resulting in the dominance of small,twining and deciduous life traits.

关键词： American forest bioclimatic indices climber life traits standart protocol species richness

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Hepatitis C virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis

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World Journal of Gastroenterology 2015年第43期21卷 12361-12369页

作者： Fahed Parvaiz Sobia Manzoor Jawed Iqbal Mehuli Sarkar-Dutta Muhammad Imran Gulam Waris Atta-urRahman School of Applied Biosciences National University of Sciences and Technology Department of Microbiology and Immunology Rosalind Franklin University of Medicine and Science

AIM: To investigate the mechanisms of insulin resistance in human hepatoma cells expressing hepatitis C virus(HCV) nonstructural protein 5A(NS5A).METHODS: The human hepatoma cell lines,Huh7 and Huh7.5,were infected with HCV or transientlytransfected with a vector expressing HCV NS5 A. The effect of HCV NS5 A on the status of the critical players involved in insulin signaling was analyzed using realtime quantitative polymerase chain reaction and Western blot assays. Data were analyzed using Graph Pad Prism version ***: To investigate the effect of insulin treatment on the players involved in insulin signaling pathway,we analyzed the status of insulin receptor substrate-1(IRS-1) phosphorylation in HCV infected cells or Huh7.5 cells transfected with an HCV NS5 A expression vector. Our results indicated that there was an increased phosphorylation of IRS-1(Ser307) in HCV infected or NS5 A transfected Huh7.5 cells compared to their respective controls. Furthermore,an increased phosphorylation of Akt(Ser473) was observed in HCV infected and NS5 A transfected cells compared to their mock infected cells. In contrast,we observed decreased phosphorylation of Akt Thr308 phosphorylation in HCV NS5 A transfected cells. These results suggest that Huh7.5 cells either infected with HCV or ectopically expressing HCV NS5 A alone have the potential to induce insulin resistance by the phosphorylation of IRS-1 at serine residue(Ser307) followed by decreased phosphorylation of Akt Thr308,Fox01 Ser256 and GSK3β Ser9,the downstream players of the insulin signalingpathway. Furthermore,increased expression of PECK and glucose-6-phosphatase,the molecules involved in gluconeogenesis,in HCV NS5 A transfected cells was ***: Taken together,our results suggest the role of HCV NS5 A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway.

关键词： Hepatitis C virus nonstructural protein 5A Insulin

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