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Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

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Journal of Cancer Metastasis and Treatment 2019年第11期4卷 47-57页

作者： Kimberley C.Agbo Jessie Z.Huang Amr M.Ghaleb Jennie L.williams Kenneth R.Shroyer Agnieszka B.Bialkowska vincent w.yang Department of Medicine Stony Brook University School of MedicineStony BrookNY 11794USA Department of Pathology Stony Brook University School of MedicineStony BrookNY 11794USA Department of Family Population and Preventive MedicineStony BrookNY 11794USA Department of Physiology and Biophysics Stony Brook University School of MedicineStony BrookNY 11794USA

Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: we found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TwIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

关键词： Krüppel-like factor 4 colorectal cancer epithelial-mesenchymal transition

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Krüppel-like factors 4 and 5:the yin and yang regulators of cellular proliferation

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Cell Research 2005年第2期15卷 92-96页

作者： Amr M.GHALEB,Mandayam O.NANDAN,Sengthong CHANCHEVALAP,w.Brian DALTON,Irfan M.HISAMUDDIN,vincent w.yang Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA Division of Digestive Diseases Department of Medicine Emory University School of Medicine Atlanta Georgia USA Department of Hematology and Oncology winship Cancer Institute Emory University School of Medicine Atlanta Georgia USA

Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverseregulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closelyrelated members of the KLF family that have a similar tissue distribution in embryos and adults. However, the two KLFsoften exhibit opposite effects on regulation of gene transcription, despite binding to similar, if not identical, cis-actingDNA sequences. In addition, KLF4 and 5 exert contrasting effects on cell proliferation in many instances; while KLF4is an inhibitor of cell growth, KLF5 stimulates proliferation. Here we review the biological properties and biochemicalmechanisms of action of the two KLFs in the context of growth regulation.

关键词： cancer cell cycle KLF transcription transformation zinc fingers.

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State of machine and deep learning in histopathological applications in digestive diseases

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world Journal of Gastroenterology 2021年第20期27卷 2545-2575页

作者： Soma Kobayashi Joel H Saltz vincent w.yang Department of Biomedical Informatics Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794United States Department of Medicine Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794United States Department of Physiology and Biophysics Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794United States

Machine learning(ML)-and deep learning(DL)-based imaging modalities have exhibited the capacity to handle extremely high dimensional data for a number of computer vision *** these approaches have been applied to numerous data types,this capacity can be especially leveraged by application on histopathological images,which capture cellular and structural features with their highresolution,microscopic ***,these methodologies have demonstrated promising performance in a variety of applications like disease classification,cancer grading,structure and cellular localizations,and prognostic predictions.A wide range of pathologies requiring histopathological evaluation exist in gastroenterology and hepatology,indicating these as disciplines highly targetable for integration of these *** have also already been primed to consider the impact of these algorithms,as development of real-time endoscopic video analysis software has been an active and popular field of *** heightened clinical awareness will likely be important for future integration of these methods and to drive interdisciplinary collaborations on emerging *** provide an overview on the application of these methodologies for gastrointestinal and hepatological histopathological slides,this review will discuss general ML and DL concepts,introduce recent and emerging literature using these methods,and cover challenges moving forward to further advance the field.

关键词： Artificial intelligence Machine learning Deep learning Gastroenterology Hepatology Histopathology

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Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 574-586页

作者： Olivier Kerdiles Méryl-Farelle Oye Mintsa Mi-mba Katherine Coulombe Cyntia Tremblay vincentÉmond Martine Saint-Pierre Clémence Rouxel Line Berthiaume Pierre Julien Francesca Cicchetti Frédéric Calon Facultéde pharmacie UniversitéLaval1050 Avenue de la MédecineQuebecQCCanada Axe Neuroscience Centre de recherche du CHU de Québec-UniversitéLaval(Pavillon CHUL)2705 Boulevard LaurierQuebecQCCanada Institute of Nutrition and Functional Foods QuebecQCCanada Optinutribrain International Associated Laboratory(NutriNeuro FranceINAFCanada)QuebecQCCanada Axe Endocrinologie et Néphrologie Centre de recherche du CHU de Québec-UniversitéLavalQuebecQCCanada Département de Médecine Facultéde MédecineUniversitéLavalQuebecQCCanada Département de Psychiatrie et Neurosciences Facultéde MédecineQuebecQCCanada

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after *** that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic ***,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal *** weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 *** this period,the animals had access to a running wheel,which they could use or *** acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars ***,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned *** to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned *** present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

关键词： 6-hydroxydopamine dopamine dopamine transporter exercise neurorestoration Parkinson’s disease polyunsaturated fatty acids omega-3

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On the Index of Finite Determinacy of Vector Fields with Resonances

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Acta Mathematica Sinica,English Series 2008年第8期24卷 1401-1408页

作者： vincent NAUDOT Jia Zhong yang Mathematics Institute University of Warwick Coventry CV4 7AL U.K. LMAM School of Mathematical Sciences Peking University Beijing 100871 P. R. China

In this paper we study normal forms for a class of germs of 1-resonant vector fields on R^n with mutually different eigenvalues which may admit extraneous resonance relations. we give an estimation on the index of finite determinacy from above as well as the essentially simplified polynomial normal forms for such vector fields. In the case that a vector field has a zero eigenvalue, the result leads to an interesting corollary, a linear dependence of the derivatives of the hyperbolic variables on the central variable.

关键词： index of finite determinacy normal forms resonance vector fields

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Soil-structure interaction on shallow rigid circular foundation:plane SH waves from far-field earthquakes

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Earthquake Engineering and Engineering Vibration 2014年第1期13卷 29-45页

作者： vincent w.Lee Hao Luo Civil & Environmental Engineering Univ. of Southern California HNTB Corporation

A closed-form wave function analytic solution of two-dimensional scattering and diffraction of incident plane SH-waves by a fl exible wall on a rigid shallow circular foundation embedded in an elastic half-space is presented. This research generalizes the previous solution by Trifunac in 1972, which tackled only the semi-circular foundation, to arbitrary shallow circular-arc foundation cases, and is thus comparatively more realistic. Ground surface displacement spectra at higher frequencies are also obtained. As an analytical series solution, the accuracy and error analysis of the numerical results are also discussed. It was observed from the results that the rise-to-span ratio of the foundation profi le, frequency of incident waves, and mass ratios of different media(foundation-structure-soil) are the three primary factors that may affect the surface ground motion amplitudes near the structure.

关键词： SH waves plane wave soil-structure interaction closed-form analytic solution Fourier-Bessel series

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Scattering and reflection of SH waves around a slope on an elastic wedged space

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Earthquake Engineering and Engineering Vibration 2019年第2期18卷 255-266页

作者： Liu Qijian wu Zhiyu vincent w Lee College of Civil Engineering Hunan University Civil and Environmental Engineering University of Southern California

The scattering and reflection of SH waves by a slope on an elastic wedged space is investigated. A series solution is obtained by using the wave function expansion method. The slope on a wedged space is divided into two subregions by an artificial, auxiliary circular arc. The wave fields with unknown complex coefficients within each sub-region are derived. Applying Graf addition theorem, the scattered waves in the sub-regions are expressed in a global coordinate system. Fourier transform is adopted to derive a consistent form of standing waves in the inner region using the orthogonality of the cosine functions. The boundary-valued problem is solved by stress and displacement continuity along the artificial, auxiliary arc to obtain the unknown complex coefficients. Parametric studies are next performed to investigate how the topography from the slope on the wedged space will affect the scattering and diffraction, and hence the amplification and de-amplification of the SH waves. Numerical results show that the surface motions on the slope of the wedged space is influenced greatly by the topography. Amplification of the surface motions near the slope vertex is significant. The corresponding phases along the wedged space surfaces are consistent with the direction that the SH waves are propagating.

关键词： earthquake ground motion wave scattering and diffraction Graf addition theorem Fourier transform

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Superfluid phases and excitations in a cold gas of d-wave interacting bosonic atoms and molecules

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Chinese Physics B 2021年第6期30卷 463-468页

作者： Zehan Li Jian-Song Pan w vincent Liu Department of Physics and Astronomy University of PittsburghPittsburghPA 15260USA wilczek Quantum Center School of Physics and Astronomy and T.D.Lee InstituteShanghai Jiao Tong UniversityShanghai 200240China

Motivated by recent advances in orbitally tuned Feshbach resonance experiments, we analyze the ground-state phase diagram and related low-energy excitation spectra of a d-wave interacting Bose gas. A two-channel model with d-wave symmetric interactions and background s-wave interactions is adopted to characterize the gas. The ground state is found to have three interesting superfluid phases: atomic, molecular, and atomic–molecular. In great contrast to what was previously known about the p-wave case, the atomic superfluid is found to be momentum-independent for the d-wave case discussed here. The Bogoliubov spectra above each superfluid phase are obtained both analytically and numerically.

关键词： d-wave interaction quantum gas Bogoliubov spectrum superfluid

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Anti-plane (SH) waves diffraction by an underground semi-circular cavity:analytical solution

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Earthquake Engineering and Engineering Vibration 2010年第3期9卷 385-396页

作者： Luo Hao vincent w. Lee Liang Jianwen HNTB Corporation Santa Ana CA 92707-8797 USA Sonny Astani Department of Civil and Environmental Engineering University of Southern California Los Angeles CA 90089-2531 USA Department of Civil Engineering Tianjin University Tianjin 300072 China

Diffraction of a two-dimensional （2D） semi-circular cavity in a half-space under incident SH-waves is studied using the classic wave function expansion method with a new de-coupling technique. This so-called ＂improved cosine half- range expansion＂ algorithm exhibits an excellent performance in reducing displacement residual errors at two rim points of concern. The governing equations are developed in a manner that minimizes the residues of the boundary conditions. Detailed derivation and analysis procedures as well as truncation of infinite linear governing equations are presented. The semi-circular cavity model presented in this paper, due to its simple profile, is expected to be used in seismic wave propagation studies as a benchmark for examining the accuracies of various analytical or numerical methods for mixed-boundary wave propagation problems.

关键词： plane SH waves diffraction, semi-circular cavity half-space improved cosine half-range expansion

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Conservation and Diversity of MicroRNA-associated Copper-regulatory Networks in Populus trichocarpa

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Journal of Integrative Plant Biology 2011年第11期53卷 879-891页

作者： Shanfa Lu Chenmin yang vincent L. Chiang Medicinal Plant Cul＇tivation Research Center Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100193 China Forest Biotechnology Group Department of Forestry and Environmental Resources College of Natural Resources North Carolina State University Raleigh NC 27695 USA

Plants develop important regulatory networks to adapt to the frequently-changing availability of copper （Cu）, However, little is known about miRNA-associated Cu-regulatory networks in plant species other than Arabidopsis. Here, we report that Cu-responsive miRNAs in Populus trichocarpa （Torr. ＆ Gray） include not only conserved miR397, miR398 and miR408, but also Populus-specific miR1444, suggesting the conservation and diversity of Cu-responsive miRNAs in plants. Copper-associated suppression of mature miRNAs is in company with the up-regulation of their target genes encoding Cu-containing proteins in Populus. The targets include miR397-targeted PtLAC5, PtLAC6 and PtLAC110a, miR398- targeted PtCSD1, PtCSD2a and PtCSD2b, miR408-targeted PtPCL1, PtPCL2, PtPCL3 and PtLAC4, and miR1444-targeted PtPP03 and PtPP06. Consistently, P. trichocarpa miR408 promoter-directed GUS gene expression is down-regulated by Cu in transgenic tobacco plants. Cu-response elements （CuREs） are found in the promoters of Cu-responsive miRNA genes. we identified 34 SQUAMOSA-promoter binding protein-like （SPL） genes, of which 17 are full-length PtSPL proteins or partial sequences with at least 300 amino acids. Phylogenetic analysis indicates that PtSPL3 and PtSPL4 are CuRE-binding proteins controlling Cu-responsive gene expression. Cu appears to be not involved in the regulation of these transcription factors because neither PtSPL3 nor PtSPL4 is Cu-regulated and no CuRE exists in their promoters.

关键词： copper Cu-response element microRNA Populus SPB domain protein.

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