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WNT/β-catenin signaling in hepatocellular carcinoma:The aberrant activation,pathogenic roles,and therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 727-746页

作者： Anna Gajos-Michniewicz malgorzata Czyz Department of Molecular Biology of Cancer Medical University of LodzLodz 92-215Poland

Hepatocellular carcinoma(HCC)is a liver cancer,highly heterogeneous both at the histopathological and molecular *** arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways,including canonical WNT/β-catenin,AKT/mTOR,MAPK pathways as well as signaling associated with telomere maintenance,p53/cell cycle regulation,epigenetic modifiers,and oxidative *** role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established,whereas in development and progression of HCC is extensively ***,we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development,acquisition of stemness features,metastasis,and resistance to *** outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in *** discuss the pivotal roles of CTNNB1 mutations,aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.

关键词： Cancer stem cells CTNNB1 mutations Liver cancer Non-coding RNA Tumor heterogeneity

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

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World Journal of Gastroenterology 2016年第41期22卷 9186-9195页

作者： Krzysztof Domagalski malgorzata Pawlowska Agnieszka Zalesna malgorzata pilarczyk Pawel Rajewski Waldemar Halota Andrzej Tretyn Centre for Modern Interdisciplinary Technologies Nicolaus Copernicus University 87-100 Toruń Poland Department of Paediatric Infectious Diseases and Hepatology Faculty of Medicine Collegium Medicum Bydgoszcz Nicolaus Copernicus University Torun 85-030 Bydgoszecz Poland Provincial Infectious Diseases Hospital in Bydgoszcz 85-030 Bydgoszecz Poland Department of Plant Physiology and Biotechnology Nicolaus Copernicus University 87-100 Toruń Poland

AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis *** We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0

关键词： Chronic hepatitis B IL28B OAS Singlenucleotide polymorphisms IFN therapy Children

从蛋白质环境引起的实际变化中剖析配体结构的误差

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上海大学学报（自然科学版） 2024年第2期30卷 229-242页

作者：乔琳琳李永乐郭聪 BICZYSKO malgorzata 上海大学理学院上海200444 上海大学量子与分子结构国际研究中心上海200444

配体构象应变能(ligand conformational strain energy,LCSE)是计算机辅助药物发现中考虑的一个重要参数.通过量子力学(quantum mechanical,QM)方法对自由态配体和蛋白质口袋中的结合态配体的结构进行计算并比较,可以获得配体构象应变能... 详细信息

配体构象应变能(ligand conformational strain energy,LCSE)是计算机辅助药物发现中考虑的一个重要参数.通过量子力学(quantum mechanical,QM)方法对自由态配体和蛋白质口袋中的结合态配体的结构进行计算并比较,可以获得配体构象应变能.然而,对配体构象应变能的合理范围以及计算方法仍然存在争议.选择8个柔性较大、特征结构模式多样的配体,这些结构的分辨率在高分辨率(0.86×10^(−10))与中等分辨率(3.10×10^(−10))之间,分别采用3种不同的量子力学方法:密度泛函(density functional theory,DFT)M062XD3、Hartree-Fock和GFN1-xTB,对8个配体进行逐步优化并计算配体能量,分析在结合态配体逐步优化到局域能量最小的自由态配体的过程中配体在结构和能量上的差异.量子力学计算结果显示,配体构象应变能小于6.0 kcal/mol,结合态配体结构中显著的几何参数误差是结合态和自由态配体结构的主要能量差异.因此,在分析配体构象应变能之前,对结合态配体结构进行精确实验测定非常重要.

关键词：蛋白质配体复合物应变能势能面密度泛函 Hartree-Fock GFN1-xTB

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美国的图论:第一个百年

数学译林 2024年第1期43卷 69-72页

作者： malgorzata Marciniak 陆柱家(译) 童欣(校) 纽约城市大学LaGuardia社区学院不详

Robin Wilson,John ***,and David ***,Graph Theory in America:The First Hundred *** University Press,2023,320 pp.,$35.怀着极大的好奇心和夏天的热情,我把这本书拿在手里.对于精装本出版物来说,它相对较轻,非常适合在休闲度假或... 详细信息

关键词： Robin 图论 Princeton

Nitrogen removal from wastewater and bacterial diversity in activated sludge at different COD/N ratios and dissolved oxygen concentrations

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Journal of Environmental Sciences 2012年第6期24卷 990-998页

作者： Magdalena Zielińska Katarzyna Bernat Agnieszka Cydzik-Kwiatkowska Joanna sobolewska Irena Wojnowska-Baryla Department of Environmental Biotechnology University of Warmia and Mazury in OlsztynS oneczna St.45G10-709 OlsztynPoland

The impact of the organic carbon to nitrogen ratio （chemical oxygen demand （COD）/N） in wastewater and dissolved oxygen （DO） concentration on carbon and nitrogen removal efficiency, and total bacteria and ammonia-oxidizing bacteria （AOB） communities in activated sludge in constantly aerated sequencing batch reactors （SBRs） was determined. At DO of 0.5 and 1.5 mg O2/L during the aeration phase, the efficiency of ammonia oxidation exceeded 90%, with nitrates as the main product. Nitrification and denitrification achieved under the same operating conditions suggested the simultaneous course of these processes. The most effective nitrogen elimination （above 50%） was obtained at the COD/N ratio of 6.8 and DO of 0.5 mg O2/L. Total bacterial diversity was similar in all experimental series, however, for both COD/N ratios of 6.8 and 0.7, higher values were observed at DO of 0.5 mg O2/L. The diversity and abundance of AOB were higher in the reactors with the COD/N ratio of 0.7 in comparison with the reactors with the COD/N of 6.8. For both COD/N ratios applied, the AOB population was not affected by oxygen concentration. Amplicons with sequences indicating membership of the genus Nitrosospira were the determinants of variable technological conditions.

关键词： nitrogen removal activated sludge COD/N ratio oxygen concentration ammonia-oxidizing bacteria microbial diversity

NO_(x) control for high-ash coal-fired power plants in India

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Clean Energy 2019年第1期3卷 24-33页

作者： malgorzata Wiatros-Motyka IEA Clean Coal Centre Apsley House176 Upper Richmond RoadLondonSW152SHUnited Kingdom

Many countries have strict emission limits for nitrogen oxides(NO_(x));thus NO_(x) control systems are widely *** has recently introduced NO_(x) emission limits,which require that pollution control technologies must be installed on most coal-fired ***,operational experience with NO_(x) control systems in India is limited to primary measures ***,Indian coals have a high level of inherent ash,which is also highly erosive and can influence the behaviour of some NO_(x) control systems and thus affect the selection *** measures for NO_(x) control from coal-fired power plants include low NO_(x) burners(LNBs),overfire air systems(OFA),fuel reburning,flue gas recirculation,fuel biasing,low excess air and combustion *** NO_(x) control includes selective catalytic reduction,selective non-catalytic reduction and multi-pollutant control *** of primary measures(LNBs and OFA)in India has been recommended to take place during next-scheduled plant outages;for many plants this could occur by ***,control strategies for individual plants will be needed to ascertain the appropriateness of installing post-combustion technologies or various combinations of NO_(x) control *** installation of secondary NO_(x) controls is not expected before test results from secondary controls on selected Indian power plants units are known.

关键词： high-ash coal NO_(x)controls SCR SNCR low NO_(x)burners overfire air India emission standards

Emissions of fluorides from welding processes

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Journal of Environmental Sciences 2015年第11期27卷 179-183页

作者： malgorzata Szewczynska Emilia Pagowska Krystyna Pyrzynska Department of Chemical and Aerosol Hazards Central Institute for Labour Protection-National Research Institute Faculty of Chemistry University of Warsaw

The levels of fluoride airborne particulates emitted from welding processes were investigated. They were sampled with the patented IOM Sampler, developed by J. H Vincent and D. Mark at the Institute of Occupational Medicine（IOM）, personal inhalable sampler for simultaneous collection of the inhalable and respirable size fractions. Ion chromatography with conductometric detection was used for quantitative analysis. The efficiency of fluoride extraction from the cellulose filter of the IOM sampler was examined using the standard sample of urban air particle matter SRM-1648 a. The best results for extraction were obtained when water and the anionic surfactant N-Cetyl-N-N-Ntrimethylammonium bromide（CTAB） were used in an ultrasonic bath. The limits of detection and quantification for the whole procedure were 8 μg/L and 24 μg/L, respectively The linear range of calibration was 0.01–10 mg/L, which corresponds to 0.0001–0.1 mg of fluorides per m3 in collection of a 20 L air sample. The concentration of fluorides in the respirable fraction of collected air samples was in the range of 0.20–1.82 mg/m3, while the inhalable fraction contained 0.23–1.96 mg/m3 of fluorides during an eight-hour working day in the welding room.

关键词： Fluorides Particle size distribution Welding processes

Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis – with impact on gastrointestinal tract

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World Journal of Gastroenterology 2021年第39期27卷 6590-6600页

作者： Izabela Berdowska malgorzata Matusiewicz Department of Biochemistry and Immunochemistry Wroclaw Medical UniversityWroclaw 50-368Lower SilesiaPoland

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembrane peptidase/serine subfamily member 2/4(TMPRSS2/4))or via receptor-mediated endocytosis(to the target cells expressing only ACE2).The second mode is associated with cysteine cathepsins(probably cathepsin L)involvement in the virus spike protein(S protein)proteolytic *** furin might activate the virus S protein enabling it to enter *** tract(GIT)involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019(COVID-19)patients exhibiting GIT symptoms,such as diarrhea,and presenting viral-shedding in *** the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT(especially brush-border enterocytes),these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive ***,in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining ***,also furin and cysteine cathepsins(cathepsin L)might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within ***,cathepsin L(due to its involvement in extracellular matrix components degradation and remodeling,the processes enhanced during SARS-CoV-2-induced inflammation)might be responsible for the dysregulation of absorption/digestion functions of GIT,thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.

关键词： COVID-19 SARS-CoV-2 Angiotensin converting enzyme 2 Transmembrane peptidase/serine subfamily member 2/4 Cathepsin L Gastrointestinal tract

A cost-effective, simple and high-throughput method for DNA extraction from insects

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Insect Science 2010年第5期17卷 465-470页

作者： malgorzata Lagisz Gordon Port Kirsten Wolff School of Biology Newcastle University Newcastle upon Tyne UK

We present a high-throughput cost-effective method to extract DNA suitable for polymerase chain reaction （PCR） from insect tissue. The method uses standard 200μL- deep 96-well plates in which samples are ground, digested and subsequently purified. The test extraction using four different insect species and controlling for potential contamination showed that the method yields good-quantity and quality DNA. PCR with mitochondrial and nuclear primers was reliable. The proposed extraction protocol combines the speed of commercial 96-well plate methods with the economies associated with readily available and cheap laboratory chemicals, consumables and equipment. Therefore, this method is particularly suitable for low-budget research projects and for laboratories with only basic equipment present.

关键词： DNA extraction genetic isolation molecular technique