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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： Joshua S.Fleishman Sunil Kumar Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory *** acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and *** curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the ***,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical *** this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic *** provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be ***,we rationalize novel targets for further translational drug discovery and provide future *** than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

Jovian Planet Influence on the Forcing of Sunspot Cycles

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World Journal of Condensed Matter Physics 2024年第1期14卷 1-9页

作者： Fred J. Cadieu Physics Department Queens College of CUNY New York USA

The history of our solar system has been greatly influenced by the fact that there is a large gas giant planet, Jupiter that has a nearly circular orbit. This has allowed relics of the early solar system formation to still be observable today. Since Jupiter orbits the Sun with a period of approximately 12 years, it has always been thought that this could be connected to the nearly 11-year periodic peak in the number of sunspots observed. In this paper, the Sun and planets are considered to be moving about a center of mass point as the different planets orbit the Sun. This is the action of gravity that holds the solar system together. The center of mass for the Jupiter-Sun system actually lies outside the Sun. The four gas giant planets dominate such effects and the four gas giant Jovian planets can be projected together to determine an effective distance from the Sun’s center. Taken together these effects do seem to function as a sunspot forcing factor with a periodicity very close to 11 years. These predictions are made without consideration of any details of what is happening in the interior of the Sun. From these estimates, sunspot cycle 25 will be expected to peak in about September-October of 2025. Sunspot cycle 26 should peak in the year March of 2037.

关键词： Sun Cycles Solar System Formation Jupiter

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Cavity continuum

Photonics Research 2024年第3期12卷 391-398页

作者： FAN CHENG VLADIMIR SHUVAYEV MARK DOUVIDZON LEV DEYCH TAL CARMON School of Electrical Engineering Tel Aviv UniversityTel Aviv 6997801Israel Physics Department Queens College of CUNYFlushingQueensNew York 11367USA Solid State Institute Technion-Israel Institute of TechnologyHaifa 3200003Israel The Graduate Center of CUNY New YorkNew York 10016USA

We experimentally demonstrate and numerically analyze large arrays of whispering gallery *** fluorescent mapping,we measure the spatial distribution of the cavity ensemble’s resonances,revealing that light reaches distant resonators in various ways,including while passing through dark gaps,resonator groups,or resonator *** spatially decays exponentially in the *** practically infinite periodic array of resonators,with a quality factor(Q)exceeding 107,might impact a new type of photonic ensembles for nonlinear optics and lasers using our cavity continuum that is distributed,while having high-Q resonators as unit cells.

关键词： resonator cavity ensemble

Measuring Impact of Lean Manufacturing Tools for Continuous Improvement on Economic Sustainability

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Journal of Systems Science and Systems Engineering 2024年第4期33卷 452-474页

作者： Luis Javier Márquez Figueroa Jorge Luis García-Alcaraz Ahmed I.Osman Alfonso Jesús Gil López Yashar Aryanfar Mika Sillanpää Mamdouh El Haj Assad Department of Electrical Engineering and Computer Science Universidad Autónoma de Ciudad JuárezCiudad JuárezChihuahuaMéxico Department of Industrial Engineering and Manufacturing Universidad Autónoma de Ciudad JuárezCiudad JuárezChihuahuaMéxico School of Chemistry and Chemical Engineering Queens UniversityBelfastNorthern IrelandUK Department of Economic and Managerial Sciences University of La RiojaLa RiojaSpain Department of Chemical Engineering University of JohannesburgJohannesburgSouth Africa Department of Sustainable and Renewable Energy Engineering University of SharjahSharjahUAE

Using Lean Manufacturing(LM)tools in production processes is crucial for companies’economic,environmental,and social sustainability *** study shows a structural equation model(SEM)that shows the relationship between LM Tools like Kaizen(KAI),Gemba(GEM),Value Stream Mapping(VSM)and Key Performance Indicator(KPI)with Economic Sustainability(ECS).Seven hypotheses were evaluated with data from 179 responses to a questionnaire about the Mexican maquiladora industry,showing that these variables are *** a 95%confidence level,the model was evaluated using the partial least squares *** findings indicate that the relationships between KAI and GEM and KAI and VSM have the strongest relationship,followed by VSM and ECS;however,VSM has the strongest effect on *** on these findings,it is recommended that managers adopt a continuous improvement(KAI)approach based on working directly on the shop floor(GEM and VSM)to support their decisions regarding economic growth(ECS).

关键词： Lean manufacturing economic sustainability structural equation model quality improvement

Sex determination in mammalian germ cells

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Asian Journal of Andrology 2015年第3期17卷 427-432页

作者： Cassy M Spiller Josephine Bowles Institute for Molecular Bioscience The University of Queens/and Brisbane QLD 4072 Australia

Germ cells are the precursors of the sperm and oocytes and hence are critical for survival of the species. In mammals, they are specified during fetal life, migrate to the developing gonads and then undergo a critical period during which they are instructed, by the soma, to adopt the appropriate sexual fate. In a fetal ovary, germ cells enter meiosis and commit to oogenesis, whereas in a fetal testis, they avoid entry into meiosis and instead undergo mitotic arrest and mature toward spermatogenesis. Here, we discuss what we know so far about the regulation of sex-specific differentiation of germ cells, considering extrinsic molecular cues produced by somatic cells, as well as critical intrinsic changes within the germ cells. This review focuses almost exclusively on our understanding of these events in the mouse model.

关键词： germ cells meiosis oocytes sex determination processes spermatozoa

A function model for the Teichmüller space of a closed hyperbolic Riemann surface

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Science China Mathematics 2019年第11期62卷 2249-2270页

作者： Yunping Jiang Department of Mathematics Queens College of the City University of New York Department of Mathematics The CUNY Graduate Center

We introduce a function model for the Teichmüller space of a closed hyperbolic Riemann *** we introduce a new metric on the Teichmüller space by using the maximum norm on the function *** prove that the identity map from the Teichmüller space equipped with the Teichmüller metric to the Teichmüller space equipped with this new metric is uniformly continuous. Moreover, we prove that the inverse of the identity, i.e., the identity map from the Teichmüller space equipped with this new metric to the Teichmüller space equipped with the Teichmüller metric, is continuous(but not uniformly). Therefore, the topology induced by the new metric is the same as the topology induced by the Teichmüller metric on the Teichmüller ***, we give a remark about the pressure metric on the function model and the Weil-Petersson metric on the Teichmüller space.

关键词： dual symbolic space geometric model function model for the Teichmüller space maximum metric

GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

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Acta Pharmaceutica Sinica B 2024年第2期14卷 698-711页

作者： Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Gastrointestinal Surgery&General Surgery the Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Thoracic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China Department of Radiation Oncology The Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 519000China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

关键词： Gastric cancer GLUL N-Cadherin β-Catenin Enzyme

Amalgamated gold-nanoalloys with enhanced catalytic activity for the detection of mercury ions(Hg^2+)in seawater samples

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Nano Research 2020年第4期13卷 989-998页

作者： Natasha Logan Claire McVey Christopher Elliott Cuong Cao Institute for Global Food Security School of Biological SciencesQueens University Belfast19 Chlorine GardensBelfastBT95DLUK Material and Advanced Technologies for Healthcare Queens University Belfast18-30 Malone RoadBelfastBT95BNUK

Mercury(Hg)is extremely toxic,and continues to cause major threats to aquatic life,human health and the ***^2+mainly derives from seawater as a product of atmospheric deposition,therefore there is great demand for sensing approaches that can detect Hg^2+in seawater ***,we demonstrate that the peroxidase-mimicking activity of gold nanoparticles(AuNPs)or so-called nanozymes,can be exploited for the detection of Hg^2+ions in various water *** a high electrolyte environment,the catalytic activity for the oxidation of 3,3’,5,5’-tetramethylbenzidine(TMB)was significantly diminished due to poor stability of the *** activity was reduced by-73.7%when the NaCl concentration was higher than 1.168%,which is much lower than that of seawater(-3.5%),thus presenting its unsuitability for detecting Hg^2+in harsh water *** overcome this limitation,AuNPs were first functionalized with oligo-ethylene glycol(OEG),of which their colloidal form presented high stability in NaCl concentrations up to 20%and across a wide range of pHs from ***,the catalytic activity of OEG-AuNPs for the oxidation of TMB was strongly suppressed by the coating,but enhanced upon formation of Au-Hg *** novel finding underlies a straightforward,sensitive,and highly selective detection platform for Hg^2+in water *** approach could detect the exposure limit level for Hg^2+in drinking water(i.e.,2 ppb for tap and bottled water)as set by the United States Environmental Protection Agency(EPA)and the World Health Organization(WHO).When Hg^2+was spiked into a 3.5%saline solution and a coastal seawater certified reference material(CRM),the detection limits were found to be 10 ancM 3 ppb,respectively,which exceed the Hg^2+concentrations commonly found within seawater(-60-80 ppb).The whole procedure takes less than 45 min to conduct,providing a highly innovative,rapid and low-cost approach for detecting Hg^2+in complex water matrices.

关键词： gold nanoparticles nanozyme peroxidase-like mercury detection w ater samples seawater

Pastoral Aspirations, Responsibilities and Strategies： A Novelist＇s Solution for the Moral Crisis in China

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Frontiers of Literary Studies in China-Selected Publications from Chinese universities 2016年第2期10卷 169-183页

作者： Yunzhong SHU Department of Classical Middle Eastern and Asian Languages and Cultures Queens College The City University of New York Queens NY 11367-1597 USA

Since the late 1970s China has implemented sweeping economic reforms for almost 40 years. At the same time, it has not officially adjusted its previous moral code. As a result, the country is now faced with a widespread moral crisis characterized by greed and anomie. To offer a remedy for this crisis in his novel The Door of the Sheep （1999）, Li Peifu, a noted writer from Henan Province, creates a village leader intent on maintaining his authoritative moral position as a shepherd by restraining his corporeal desires and exercising his authority on his flock and for his flock. In a subsequent novel entitled pervasive moral disorientation in a village where nobody assumes a pastoral position. The present article analyzes these two novels in connection with the sociopolitical environment of contemporary China. Special attention will be paid to Li＇s interpretation of human selfishness as the root cause of the moral crisis and his attempt to offer a politically feasible and morally effective solution.

关键词： Li Peifu moral crisis human selfishness pastoral position,self-restraint