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NT157 has antineoplastic effects and inhibits IrS1/2 and STAT3/5 in JAK2^(V617F)-positive myeloproliferative neoplasm cells

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2440-2449页

作者： Bruna Alves Fenerich Jaqueline Cristina Fernandes Ana Paula Nunes rodrigues Alves Juan Luiz Coelho-Silva renata Scopim-ribeiro Priscila Santos Scheucher Christopher A.Eide Cristina E.Tognon Brian J.Druker Eduardo magalh.es rego João Agostinho Machado-Neto Fabiola Traina Department of Medical Images Hematologyand Clinical OncologyUniversity of Sao Paulo at Ribeirao Preto Medical SchoolRibeirao PretoSao PauloBrazil Center for Cell-Based Therapy Sao Paulo Research FoundationRibeirao PretoSao PauloBrazil Knight Cancer Institute Oregon Health&Science UniversityPortlandORUSA Howard Hughes Medical Institute PortlandORUSA Department of Internal Medicine University of Sao Paulo Medical SchoolSao PauloBrazil Department of Pharmacology Institute of Biomedical Sciences of the University of Sao PauloSao PauloBrazil

recent data indicate that IGF1r/IrS signaling is a potential therapeutic target in BCr-ABL1-negative myeloproliferative neoplasms(MPN);in this pathway,IrS2 is involved in the malignant transformation induced by JAK2^(V617F),and upregulation of IGF1r signaling induces the MPN ***157,a synthetic compound designed as an IGF1r-IrS1/2 inhibitor,has been shown to induce antineoplastic effects in solid ***,we aimed to characterize the molecular and cellular effects of NT157 in JAK2^(V617F)positive MPN cell lines(HEL and SET2)and primary patient hematopoietic *** JAK2^(V617F)cell lines,NT157 decreased cell viability,clonogenicity,and cell proliferation,resulting in increases in apoptosis and cell cycle arrest in the G2/M phase(preatment inhibited IrS1/2,JAK2/STAT,and NFκB signaling,and it activated the AP-1 complex,downregulated four oncogenes(CCND1,MYB,WT1,and NFKB1),and upregulated three apoptotic-related genes(CDKN1A,FOS,and JUN)(press in a JAK2/STAT-independent ***157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients(pese findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IrS1/2 proteins may represent a promising therapeutic strategy for MPN.

关键词： JAK2 IGF1r neoplasms STAT3

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Characterization and source apportionment of volatile organic compounds in Hong Kong:A 5-year study for three different archetypical sites

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Journal of Environmental Sciences 2025年第5期151卷 424-440页

作者： Yuchen Mai Vincent Cheung Peter K.K.Louie Kenneth Leung Jimmy C.H.Fung Alexis K.H.Lau Donald r.B.lake Dasa Gu Division of Environment and Sustainability The Hong Kong University of Science and TechnologyHong Kong 999077China Environmental Protection Department Hong Kong 999077China Environment and Ecology Bureau Hong Kong 999077China Department of Chemistry University of CaliforniaIrvine 92617USA

Initial success has been achieved in Hong Kong in controlling primary air pollutants,but ambient ozone levels kept increasing during the past three *** organic compounds(VOCs)are important for mitigating ozone pollution as its major *** study analyzed VOC characteristics of roadside,suburban,and rural sites in Hong Kong to investigate their compositions,concentrations,and source *** showthat the TVOC concentrations were 23.05±13.24,12.68±15.36,and 5.16±5.48 ppbv for roadside,suburban,and rural sites between May 2015 to June 2019,*** using Positive Matrix Factorization(PMF)model,six sources were identified at the roadside site over five years:Liquefied petroleum gas(LPG)usage(33%–46%),gasoline evaporation(8%–31%),aged air mass(11%–28%),gasoline exhaust(5%–16%),diesel exhaust(2%–16%)and fuel filling(75–9%).Similarly,six sources were distinguished at the suburban site,including LPG usage(30%–33%),solvent usage(20%–26%),diesel exhaust(14%–26%),gasoline evaporation(8%–16%),aged air mass(4%–11%),and biogenic emissions(2%–5%).At the rural site,four sources were identified,including aged airmass(33%–51%),solvent usage(25%–30%),vehicular emissions(11%–28%),and biogenic emissions(6%–12%).The analysis further revealed that fuel filling and LPG usage were the primary contributors to OFP and OH reactivity at the roadside site,while solvent usage and biogenic emissions accounted for almost half of OFP and OH reactivity at the suburban and rural sites,*** findings highlight the importance of identifying and characterizing VOC sources at different sites to help policymakers develop targeted measures for pollution mitigation in specific areas.

关键词： Volatile organic compounds Positive matrix factorization Source apportionment Ozone formation

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The landscape epidemiology of echinococcoses

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Infectious Diseases of Poverty 2016年第1期5卷 107-119页

作者： Angela M.Cadavid restrepo Yu rong Yang Donald P.McManus Darren J.Gray Patrick Giraudoux Tamsin S.Barnes Gail M.Williams ricardo J.Soares magalh.es Nicholas A.S.Hamm Archie C.A.Clements research School of Population Health The Australian National UniversityCanberraNew South WalesAustralia Ningxia Medical University YinchuanNingxia Hui Autonomous RegionP.R.China Molecular Parasitology Laboratory QIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia Chrono-environment lab UMR6249University of Bourgogne Franche-Comté/CNRSBesançonFrance Institut Universitaire de France ParisFrance The University of Queensland School of Veterinary ScienceGattonQueenslandAustralia The University of Queensland Queensland Alliance for Agriculture and Food InnovationGattonQueenslandAustralia School of Public Health The University of QueenslandBrisbaneQueenslandAustralia Child Health research Centre The University of QueenslandBrisbaneQueenslandAustralia Faculty of Geo-Information Science and Earth Observation(ITC) University of TwenteEnschedeThe Netherlands

Echinococcoses are parasitic diseases of major public health importance *** infection results in chronic disease with poor prognosis and serious medical,social and economic consequences for vulnerable *** to recent estimates,the geographical distribution of Echinococcus *** is expanding and becoming an emerging and re-emerging problem in several regions of the *** endemicity is geographically heterogeneous and over time it may be affected by global environmental ***,landscape epidemiology offers a unique opportunity to quantify and predict the ecological risk of infection at multiple spatial and temporal ***,we review the most relevant environmental sources of spatial variation in human echinococcosis risk,and describe the potential applications of landscape epidemiological studies to characterise the current patterns of parasite transmission across natural and human-altered *** advocate future work promoting the use of this approach as a support tool for decision-making that facilitates the design,implementation and monitoring of spatially targeted interventions to reduce the burden of human echinococcoses in disease-endemic areas.

关键词： Landscape epidemiology Helminth infection Human echinococcosis Echinococcus spp Environmental change Geographic information systems remote sensing Geostatistics

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Treatability studies of naphthalene in soil,water and air with persulfate activated by iron(Ⅱ)

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Journal of Environmental Sciences 2020年第4期32卷 67-77页

作者： Gabriela P.Mendes Vivian M.A.magalh.es Lélia C·r·Soares rayanne M.Aranha Claudio A.O.Nascimento Marilda M.G.r.Vianna Osvaldo Chiavone-Filho Department of Chemical Engineering University of Sao PauloSPf 05508-000Brazil Department of Chemical Engineering Federal University of Rio Grande Do NorteNatalRN59072-970Brazil

Chemical oxidation was applied to an artificially contaminated soil with naphthalene(NAP).Evaluation of NAP distribution and mass reduction in soil,water and air phases was carried out through mass *** of NAP distribution and mass reduction in soil,water and air phases was carried out through mass *** importance of the air phase analysis was emphasized by demonstrating how NAP behaves in a sealed system over a 4 hr reaction *** of Experiments method was applied to the following variables:sodium persulfate concentration[SP],ferrous sulfate concentration[Fes04],and *** system operated with a prefixed solid to liquid ratio of 1:*** following conditions resulted in optimum NAP removal[SP]=18.37 g/L,[FesO4]=4.25 g/L and pH=*** the end of the 4 hr reaction,62%of NAP was *** the soil phase,the chemical oxidation reduced the NAP concentration thus achieving levels which comply with Brazilian and USA environmental *** the NAP partitioning view,the monitoring of each phase allowed the variabilities assessment over the process,refining the knowledge of mass *** on NAP distribution in the system,this study demonstrates the importance of evaluating the presence of semi-volatile and volatile organic compounds in the air phase during remediation,so that there is greater control of the system as to the distribution and presence of the contaminant in the *** results highlight the importance of treating the contaminant in all its phases at the contaminated site.

关键词： Chemical oxidation Phase distribution Degradation kinetics PAH Soil remediation Mass balance

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The evolutionarily diverged single-stranded DNA-binding proteins SSB1/SSB2 differentially affect the replication,recombination and mutation of organellar genomes in Arabidopsis thaliana

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Plant Diversity 2025年第1期47卷 127-135页

作者： Weidong Zhu Jie Qian Yingke Hou Luke r.Tembrock Liyun Nie Yi-Feng Hsu Yong Xiang Yi Zou Zhiqiang Wu Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China Guangdong Laboratory for Lingnan Modern Agriculture College of Life SciencesSouth China Agricultural UniversityGuangzhou 510642China School of Life Sciences Southwest UniversityChongqing 400715China Department of Biology Colorado State UniversityFort CollinsCO 80523USA School of Medical Molecular and Forensic SciencesMurdoch UniversityMurdochWA 6149Australia State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China Shenzhen research Institute of Henan University Shenzhen 518000China

Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA *** Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still *** this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed *** on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both *** findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.

关键词： SSB Organellar genomes replication recombination Mutation

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Prospective Study on the results of the Tuboplasty in rural region in Germany

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International Journal of Otolaryngology and Head & Neck Surgery 2025年第1期14卷 1-11页

作者： Peter r. Issing Hendrik Tebben Emad Alsabbagh Christian Issing Department of Otorhinolaryngology Head- Neck- and Facial Plastic Surgery Klinikum Bad Hersfeld GmbH Bad Hersfeld Germany Department of Ophthalmology Klinikum Bad Hersfeld GmbH Bad Hersfeld Germany Department of Otorhinolaryngology Johann-Wolfgang von Goethe University Frankfurt Germany

1) Introduction: Ventilation disorders of the middle ear play a major role in everyday clinical ENT-practice and sometimes represent a major therapeutic challenge. In addition to the conventional therapy of tympanostomy tube insertion, tuboplasty (TP) offers a less invasive option for treating this problem. The study should examine whether TP can be performed in a rural setting. 2) Material and methods: This is a prospective, monocentric study of patients scheduled for TP because of tubal ventilation disorder (TVD) in a rural region of Germany. The diagnosis was established after a thorough clinical examination and by assessing the possibility of performing the Valsalva maneuver, the tympanogram type, recording the middle ear pressure and air-bone gap. The subjective impairment caused by the TVD was evaluated using the EDTQ-7 questionnaire pre- and approximately 3 months postoperatively. 3) results: Sixty-two patients with 92 TP were included with a mean age of 44.1 years. The EDTQ-7 score decreased highly significantly from 3.6 to 1.7 (p rrelating with parameters such as age, sex, BMI, allergies or smoking. Middle ear pressure fell in average by −87 daPa, resulting in an improvement of the tympanogram type. The preoperative air-bone gap of 10.2 dB also was reduced significantly in most patients to 8.0 dB after the procedure. No notable complications occurred beside a sore throat due to the use of a laryngeal mask for ventilation during anesthesia in two cases. 4) Conclusion: In our experience, TP represents a less invasive and, in many cases, successful alternative to the established tympanostomy tube insertion with the advantage of an intact eardrum. It can also be offered and successfully performed in a rural setting.

关键词： Eustachian Tube Dysfunction Tuboplasty Eustachian Tube Valsalva Maneuver Grommet

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dP/dt_(max):An underestimated prognostic factor in large animal infarction model

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Animal Models and Experimental Medicine 2025年第1期8卷 171-178页

作者： rita Garamvölgyi Dénes Kőrösi OttóTátrai Emőke Bodor Dániel Fajtai Kornélia Farkas András Vorobcsuk Doctoral School in Animal Science Hungarian University of Agriculture and Life SciencesKaposvárHungary Department of Cardiology Kaposi Moritz Teaching HospitalKaposvárHungary Medicopus Nonprofit Ltd. KaposvárHungary Institute of Bioanalysis Medical SchoolUniversity of PécsPécsHungary Doctoral School of Clinical Medicine University of PécsPécsHungary

The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon *** monitor the cardiac function,measurements were made by cardiac magnetic resonance imaging(cMrI),invasive pressure monitoring,and a Pulse index Continuous Cardiac Output(PiCCO)hemo-dynamic system at 0,72,and 720 h during the follow-up ***-diastolic and end-systolic volumes(EDV,esV),left ventricular ejection fraction(LVEF)obtained by cMrI evaluation,global ejection fraction and aortic dP/dt_(max)obtained by the invasive method,were recorded and *** 72-and 720-h EDV data showed a signifi-cant increase(p=0.012,red to baseline,and the Day 30 data showed a significant increase compared to Day 3(p=0.022).The esV 72 h after the infarction showed a significant increase(p=0.001)compared to baseline,which did not change significantly by Day 30(p=0.781)compared to Day *** and esV were signifi-cantly negatively correlated with aortic dp_(max),and esV was significantly correlated with *** LVEF and dP_(max),a significant(prsening was demonstrated at Day 3 compared to baseline,which was no longer statistically de-tectable for LVEF at Day 30(p=0.141),while the difference for dP_(max)was maintained(p=0.002).The complementary use of PiCCO hemodynamic measurements in large animal models makes the previously used methodologies more robust and reliable.

关键词： dp/dt_(max) hemodynamic measurements infarction model minipig PiCCO

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Health anxiety and work loss in patients diagnosed with serrated polyposis syndrome:A cross sectional study

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World Journal of Clinical Oncology 2025年第2期16卷 52-62页

作者： Angus Thompson Natalie r Dierick Louise Heiniger Stuart N Kostalas School of Clinical Medicine University of New South WalesPort Macquarie 2444New South WalesAustralia Department of Gastroenterology Port Macquarie GastroenterologyPort Macquarie 2444New South WalesAustralia

BACKGrOUND Serrated polyposis syndrome(SPS)is a polyposis condition with neoplastic potential,but its psychological impact is not well *** To assess health anxiety prevalence in a regional Australian cohort of SPS patients and explore factors influencing it,including workforce impacts of regular *** This cross-sectional study screened patients aged 18-65 undergoing colonoscopy in a regional gastroenterology practice between January 2015 and June *** SPS patients were invited to *** included the Short Health Anxiety Inventory,employment status,and previous demographic and medical *** Health anxiety was found in 21.57%of SPS patients,with anxious patients being significantly more concerned about surveillance(Or=7.70).Patients lost an average of 11.04 work hours per *** Health anxiety in SPS patients aligns with rates in other gastroenterology *** it may improve management,though further research is needed to better understand prevalence and care improvements.

关键词： Serrated polyposis syndrome Health anxiety Colorectal cancer Surveillance

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Fluid Leakage in Submerged Offshore Pipeline: An Analysis of Oil Dispersion in Seawater

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Open Journal of Fluid Dynamics 2020年第2期10卷 95-121页

作者： Gicelia Moreira Hortência L. Fernandes magalh.es Daniela P. Simões de Almeida Tavares Balbina r. de Brito Correia Boniek E. Leite Adriana B. da Costa Pereira Severino r. de Farias Neto Antonio G. Barbosa de Lima Department of Chemical Engineering Federal University of Campina Grande Campina Grande Brazil

Leakages in oil pipelines can cause financial losses and several environmental damages, where large-scale offshore oil and gas exploration results in large releases of oil and gas into ocean waters. In the event of oil leakage, an immediate and adequate response is required to reduce environmental damage, such as containment barriers, for example, which depends on the agglomeration of oil particles, velocity and tendency to propagation. Thus, the understanding of the fluid flow behavior around of subsea pipeline at different depths is crucial. On the other hand, the knowledge of interfacial phenomena of immiscible liquids allows the process of adjective migration in submarine pipelines. Consequently, this science enables the prediction of the behavior and the geometric shape of the water-oil interface and provides a phenomenological foundation concerning the theories of perturbation, the stability criteria and mathematical modeling, as well as the flow patterns in the neighborhoods and submerged pipelines. From this perspective, this work aims to study the oil dispersion in sea water caused by leakage in a submerged pipeline. Here, a two-dimensional mathematical model based on the mass and linear momentum conservation equations and the standard k-ε turbulence model, was developed. The dynamic behavior of the oil and water phases is evaluated by pressure fields, surface velocity, volumetric fraction and velocity vectors. Simulation results show the presence of oil flux from the pipe to the marine stream and vice-versa. Further, the increase in oil velocity at the pipe inlet leads to an increase in pressure drop.

关键词： Computational Fluid Dynamics Submerged Offshore Pipeline Leakage CFX

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Occurrence and Distribution of Antifouling Biocide Diuron along the Coastal Areas of Zanzibar Island

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Journal of Geoscience and Environment Protection 2025年第1期13卷 1-17页

作者： Hassan r. Ali Fatma Kh. Ali Miza A. Kombo School of Natural and Social Sciences The State University of Zanzibar Zanzibar Tanzania Tropical research Centre for Oceanography Environment and Natural Resources The State University of Zanzibar Zanzibar Tanzania Karume Institute of Science and Technology Mbweni Zanzibar Tanzania

Diuron (N-(3,4-dichlorophenyl)-N,N-dimethylurea) is one among the booster biocides substituted tributyltin as an antifouling agent. It has continued to be used ever since, though little is known about their levels in the maritime setting of Zanzibar. This paper details the occurrence and distribution of diuron around the coastline of Zanzibar Island. The reported concentrations of diuron in water ranged from Below Detection Limit to 1321.67 ± 52.3 ng/L at Bwawani. Majority of the sites showed levels above Environmental risk Limit of 430 ng/L as proposed by the Dutch Authorities. The findings suggest the contamination is elevated especial in Harbor, Bwawani, Chapwani and even at Marine Protected Areas such Mnemba Island where the value of 620.33 ± 5.70 ng/L was recorded. The main possible sources of the contamination are cargo shipping, passenger speedboats, fishing, and tourism activities taking places in these areas. Therefore, future studies on the antifouling biocide diuron particularly on long term monitoring, chronic exposure, risk assessment, organisms’ responses and pollution models will add special value towards better understanding of the mechanisms and sustainable marine ecosystem health.

关键词： Diuron Coral reefs Harbor Marine resources Marine Protected Areas

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