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Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-βpathway

Signal Transduction and Targeted Therapy 2020年第1期5卷 1732-1743页

作者： Xiaoxue Yang Liping Ma Rong Wei Tinghong Ye JianKang Zhou Maoyao Wen Ruoting Men rami i.aqeilan Yong Peng Li Yang Department of Gastroenterology&Hepatology West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Biotherapy and Cancer Centre West China HospitalSichuan Universityand Collaborative Innovation Centre for BiotherapyChengdu 610041China School of Bioscience and Technology Chengdu medical collegeChengdu 610500China Department of immunology&Cancer Research Hebrew University-Hadassah Medical SchoolJerusalemIsrael

The activation of hepatic stellate cells(HSCs)participates in liver fibrosis,and emerging evidences indicate that microRNAs(miRNAs)are abnormally expressed during HSC activation.However,the potential roles of miRNAs in liver fibrosis still remain elusive.Therefore,this study aimed to investigate the role of miR-199a-3p in liver fibrosis and its underlying mechanism.We found that miR-199a-3p expression was dramatically upregulated during HSC activation in vitro,and during liver fibrogenesis in CCl4-treated rats,and its liver expression was increased in the patients with cirrhosis.By the luciferase assay and RT-qPCR,we revealed that the expression of miR-199a-3p in HSCs was driven by the transcription factor Twist1 which could be further induced by TGF-βtreatment.Functional studies showed that inhibition of miR-199a-3p in both human LX2 cells and rat HSCs significantly decreased the expression of fibrotic markers,such as fibronectin and connective tissue growth factor(CTGF),whereas the forced expression of miR-199a-3p exhibited opposite effects,demonstrating the role of miR-199a-3p in promoting HSC activation.Mechanistically,miR-199a-3p plays an important role in TGF-βsignalling pathway activation through targeting CAV2 that negatively regulates the expression of transforming growth factor-beta receptor type i(TGFβRi).importantly,administration of antagomiR-199a-3p in the CCl4-treated mice significantly ameliorated hepatic fibrosis.in conclusion,Twist1-induced miR-199a-3p mediates the activation of HSCs by suppressing CAV2 expression and subsequently increasing TGFβRi expression to promote TGF-βpathway.Our findings highlight the therapeutic potential of miR-199a-3p for hepatic fibrosis.

关键词： Twist1 miR hepatic

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Pleiotropic tumor suppressor functions of WWOX antagonize metastasis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2033-2042页

作者： Saleh Khawaled Giovanni Nigita Rosario Distefano Sara Oster Sung-Suk Suh Yoav Smith Abed Khalaileh Yong Peng Carlo M.Croce Tamar Geiger Victoria L.Seewaldt rami i.aqeilan Lautenberg Center for immunology and Cancer Research Hebrew University-Hadassah Medical SchoolIMRICJerusalemIsrael Department of Cancer Biology and Genetics Wexner Medical CenterThe Ohio State UniversityColumbusOHUSA Department of Bioscience Mokpo National UniversityMuanRepublic of Korea Genomic Data Analysis Unit Hebrew University-Hadassah Medical SchoolJerusalemIsrael Department of Surgery Hadassah Medical CenterJerusalemIsrael Department of Thoracic Surgery State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041 ChengduChina Department of Human Molecular Genetics and Biochemistry Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Population Sciences City of Hope Comprehensive Cancer CenterDuarteCAUSA

Tumor progression and metastasis are the major causes of death among cancer associated mortality.Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition(EMT).Acquirement of these various hallmarks rely on different cellular pathways,including TGF-βand Wnt signaling.Recently,we reported that WW domain-containing oxidoreductase(WWOX)acts as a tumor suppressor and has anti-metastatic activities involving regulation of several key microRNAs(miRNAs)in triple-negative breast cancer(TNBC).Here,we report that WWOX restoration in highly metastatic MDA-MB435S cancer cells alters mRNA expression profiles;further,WWOX interacts with various proteins to exert its tumor suppressor function.Careful alignment and analysis of gene and miRNA expression in these cells revealed profound changes in cellular pathways mediating adhesion,invasion and motility.We further demonstrate that WWOX,through regulation of miR-146a levels,regulates SMAD3,which is a member of the TGF-βsignaling pathway.Moreover,proteomic analysis of WWOX partners revealed regulation of the Wnt-signaling activation through physical interaction with Disheveled.Altogether,these findings underscore a significant role for WWOX in antagonizing metastasis,further highlighting its role and therapeutic potential in suppressing tumor progression.

关键词： WWOX metastasis suppressor

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Enhancing the Decomposition of Paper Cups Using Galleria Mellonella and Eisenia Fetida

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Journal of Renewable Materials 2024年第2期12卷 349-367页

作者： Shadi Moqbel Habib Al-Ghoul Abd Al-Majeed Al-Ghzawi rami Mukbel Civil Engineering Department The University of JordanAmman11942Jordan Department of Chemistry Technical University of MunichMunichGermany Plant Production Jordan University of Science and TechnologyIrbid22110Jordan Basic Medical Veterinary Sciences Jordan University of Science and TechnologyIrbid22110Jordan

The composition of paper cups creates a challenge for the recycling industry,as the paperboard–plastic film composite is hard to separate.Therefore,paper cups are sent to landfills or waste incinerators.This study explores the combined use of red worms(Eisenia fetida)and Greater wax moth(Galleria mellonella)in the biodegradation of paper cups.The study investigates the conditions and combinations that promote using Eisenia fetida and Galleria mellonella for degrading paper cups.The study considered the influence of environmental temperature,the presence of food waste,varying the number of Eisenia fetida worms,and the presence of a Galleria mellonella growth-slowing agent on the degradation process.To achieve the study objectives,the study followed a quantitative approach.The study monitored the degradation of paper cup cuts that were placed in jars containing different combinations of Eisenia fetida worms,Galleria mellonella larvae,food waste,bedding material,and Galleria mellonella growth-slowing agents.The study found that the best operating temperature is 30oC.The study found that using food waste improves the performance of Eisenia fetida worms and Galleria mellonella larvae significantly.The study found that adding a Galleria mellonella growth-slowing agent slightly enhances the degradation of the paper cup.Finally,a numerical model was obtained to simulate the paper cup degradation efficiency.

关键词： Paper cups resource recovery recycling circular economy Galleria mellonella Eisenia fetida

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Non-Uniform Pion Tetrahedron Aether and Electron Tetrahedron Model

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第2期10卷 810-824页

作者： rami Rom independent Researcher Zikhron-Yaakov Israel

We propose that the QCD vacuum pion tetrahedron condensate density vary in space and drops to extremely low values in the Kennan, Barger and Cowie (KBC) void in analogy to earth’s atmospheric density drop with elevation from earth. We propose a formula for the gravitation acceleration based on the non-uniform pion tetrahedron condensate. Gravity may be due to the underlying microscopic attraction between quarks and antiquarks, which are part of the vacuum pion tetrahedron condensate. We propose an electron tetrahedron model, where electrons are comprised of tetraquark tetrahedrons, and . The quarks determine the negative electron charge and the or quarks determine the electron two spin states. The electron tetrahedron may perform a high frequency quark exchange reactions with the pion tetrahedron condensate by tunneling through the condensation gap creating a delocalized electron cloud with a fixed spin. The pion tetrahedron may act as a QCD glue bonding electron pairs in atoms and molecules and protons to neutrons in the nuclei. Conservation of valence quarks and antiquarks is proposed.

关键词： Standard Model (SM) QCD Vacuum Condensate Electric Dipole Moment (EDM) KBC Void Antimatter MOND Theory Aether

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The Pionic Deuterium and the Pion Tetrahedron Vacuum Polarization

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第1期10卷 329-345页

作者： rami Rom Zikhron-Ya’akov Israel

A double-well potential model is proposed for the pionic deuterium that enables to calculate the energy split, the potential barrier height and estimate the pion tetrahedron edge length. We propose that pion tetrahedrons, πTd = ud~dũ, play a central role in the Yukawa interaction by enabling quark exchange reactions between protons and neutrons by tunneling through a potential barrier. A vacuum polarization Feynman diagram is proposed for the πTd having chains of fermion loops for the two valence quarks and anti-quarks connected by gluons. With a higher order vacuum polarization diagram, the d and u quark loops are interleaved and the chiral symmetry is broken dynamically. The proposed πTd vacuum polarization integral does not diverge in both the iR and UV limits and vanishes in the limit of an infinite pion tetrahedron condensate. We propose a new Delbruck scattering Feynman diagram that includes d and u quark and anti-quark interleaved loops. We further propose that conversion of gravitons to photons may occur via quark and anti-quark loops that describe the pion tetrahedrons dynamics in the vacuum and may also transfer gravitational waves.

关键词： Pionic Deuterium (πD) Yukawa interaction QCD Vacuum Double-Well Potential Chiral Perturbation Theory Vacuum Polarization Gravitational Waves

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Detection of 4p16.3 deletion and 11p15.5p15.4 gain in a boy by comparative genomic hybridization array:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1517-1522页

作者： işın Kaya Medical Genetics Bakırçay UniversityÇiğli Education ve Training Hospitalİzmir 35620Turkey

BACKGROUND Nonallelic homologous recombination(NAHR)of segmental duplications or low copy repeats(LCRs)result in DNA gain/loss and play an important role in the origin of genomic disorders.CASE SUMMARY A 3-year-old boy was referred for genetic analysis.Comparative genomic hybrid-ization array analysis revealed a loss of 3776 kb in the 4p16.3 chromosomal region and a gain of 3201 kb in the 11p15.5p15.4 chromosomal region.CONCLUSiON Genomic imbalances caused by NAHR in LCRs result in deletion and duplication syndromes.

关键词： Wolf-Hirschhorn syndrome Silver-Russell syndrome Recurrent rearrangements Case report

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Taxonomy,distribution,and contemporary exposure of terrestrial mammals to floods and human pressure across different areas for biodiversity conservation in China

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integrative Zoology 2024年第3期19卷 458-467页

作者： Roman SHARNUUD Eric i.AMECA MOE Key Laboratory for Biodiversity Science&Ecological Engineering College of Life SciencesBeijing Normal UniversityBeijingChina Climate Change Specialist Group Species Survival CommissionInternational Union for Conservation of NatureGlandSwitzerland

A significant research focus is placed on identifying animal species and areas at future risk to human-induced alterations of the environment and long-term changes in climatic conditions.Yet,the extent to which exposure to extreme climatic events and intense human pressure can increase the risk of harmful impacts on species remains poorly investigated.Focusing on terrestrial mammals in China,one of the world’s megadiverse countries,we investigated patterns of contemporary exposure to floods and human pressures and determined their taxonomic representation and distribution across three major area-based conservation schemes,namely,national nature reserves(NNRs),priority areas for biodiversity conservation(PABCs),and key biodiversity areas(KBAs).Among the 440 species assessed with moderate or high exposure to floods,327(∼75%)also qualified as moderate or high in exposure to intense human pressure.These species mainly belong to the orders Chiroptera,Eulipotyphla,and Rodentia.Likewise,there were 305,311,and 311 species with moderate or high exposure to flood and intense human pressure represented across NNRs,PABCs,and KBAs,respectively.Our findings support the prioritization of KBAs for expansion of site-based protection efforts such as NNRs in China,considering threats to species from exposure to adverse effects from both extreme climate and human pressure.

关键词： conservation floods human pressure mammals taxonomy

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Are population cycles recovering?

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integrative Zoology 2024年第3期19卷 538-547页

作者： Vasily D.YAKUSHOV Boris i.SHEFTEL A.N.Severtsov institute of Ecology and Evolution of the Russian Academy of Sciences MoscowRussia

The dynamics of populations of small mammals of Central Siberia was analyzed.The studies were carried out at the Yenisei ecological station“Mirnoye”of the A.N.Severtsov institute of Ecology and Evolution,Russian Academy of Sciences.The time series analysis was performed by the wavelet transform using the statistical data processing language R.in the 20th century,the dynamics of the population of the community and some of its constituent species(Sorex araneus;S.caecutiens;S.isodon;S.tundrensis;S.minutus;Craseomys rufocanus;Clethrionomys rutilus;Microtus oeconomus;M.agrestis)were characterized by a 4-year periodicity.The type of dynamics changed to noncyclic by the nineties,but by 2022,four species(S.araneus,S.isodon,C.rutilus,and M.oeconomus)and the community as a whole showed a tendency toward recovery of population cycles.The remaining species were characterized by consistently low numbers with irregular low amplitude fluctuations.

关键词： population cycles small mammals time-series analysis wavelet transform

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基于嵌入式网格的裂缝性致密油储层压裂生产一体化数值模拟方法

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计算物理 2024年

作者：徐世乾郭建春 Younis M.rami 卢聪 Texas A&M University Harold Vance Department of Petroleum Engineering College Station 西南石油大学油气藏地质及开发工程国家重点实验室

有效的一体化模拟裂缝性致密油储层压裂生产过程是评价压裂设计的关键之一。为此，基于嵌入式网格的基质裂缝全域空间流固耦合数值模拟方法，进一步考虑天然裂缝影响下裂缝动态扩展、低速非线性渗流、基质与裂缝应力敏感，实现了裂缝性... 详细信息

有效的一体化模拟裂缝性致密油储层压裂生产过程是评价压裂设计的关键之一。为此，基于嵌入式网格的基质裂缝全域空间流固耦合数值模拟方法，进一步考虑天然裂缝影响下裂缝动态扩展、低速非线性渗流、基质与裂缝应力敏感，实现了裂缝性致密油储层压裂生产一体化多机理模拟。进而分析了天然裂缝、非线性渗流对裂缝扩展及生产动态的一体化影响规律。研究结果表明：模型可以在生产过程中任意时刻模拟压裂，为重复压裂、加密井的设计分析提供了有效工具。当基质岩石的抗拉强度由10.2 MPa降到2.3 MPa时，破碎带逐渐增大，滤失作用增加，导致主裂缝长度降低8%-9%，但可以增加累产油量17.5%至61.1%，影响作用显著且主要影响早期的日产油量。与启动压力梯度模型相比，低速非线性渗流可以更好地预测致密油生产动态。该方法为裂缝性致密油储层压裂生产一体化的动态预测、规律分析、工艺优化提供了高效工具。

关键词：致密油裂缝性储层流固耦合压裂生产一体化嵌入式网格

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Using fracture-based continuum modeling of coupled geomechanical-hydrological processes for numerical simulation of hydraulic fracturing

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第5期16卷 1582-1599页

作者： Goodluck i.Ofoegbu GNO Modeling Research LLC. San AntonioTX78253USA

This paper describes numerical simulation of hydraulic fracturing using fracture-based continuum modeling(FBCM)of coupled geomechanical-hydrological processes to evaluate a technique for high-density fracturing and fracture caging.The simulations are innovative because of modeling discrete fractures explicitly in continuum analysis.A key advantage of FBCM is that fracture initiation and propagation are modeled explicitly without changing the domain grid(i.***.no re-meshing).Further,multiple realizations of a preexisting fracture distribution can be analyzed using the same domain grid.The simulated hydraulic fracturing technique consists of pressurizing multiple wells simultaneously:initially without permeating fluids into the rock,to seed fractures uniformly and at high density in the wall rock of the wells;followed by fluid injection to propagate the seeded fracture density hydraulically.FBCM combines the ease of continuum modeling with the potential accuracy of modeling discrete fractures and fracturing explicitly.Fractures are modeled as piecewise planar based on intersections with domain elements;fracture geometry stored as continuum properties is used to calculate parameters needed to model individual fractures;and rock behavior is modeled through tensorial aggregation of the behavior of discrete fractures and unfractured rock.Simulations are presented for previously unfractured rock and for rock with preexisting fractures of horizontal,shallow-dipping,steeply dipping,or vertical orientation.Simulations of a single-well model are used to determine the pattern and spacing for a multiple-well design.The results illustrate high-density fracturing and fracture caging through simultaneous fluid injection in multiple wells:for previously unfractured rock or rock with preexisting shallow-dipping or horizontal fractures,and in situ vertical compressive stress greater than horizontal.if preexisting fractures are steeply dipping or vertical,and considering the same in situ stress condition,well pressurization without fl

关键词： Discrete fracture Fracture-based continuum modeling Fracture caging High-density fracturing Hydraulic fracturing Preexisting fracture

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