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Dual activities of a silencing information regulator complex in yeast transcriptional regulation and DNA-damage response

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mLife 2024年第2期3卷 207-218页

作者： josephine Rybchuk Wei Xiao Department of Biochemistry Microbiology and ImmunologyUniversity of SaskatchewanSaskatoonSaskatchewanCanada Toxicology Program University of SaskatchewanSaskatoonSaskatchewanCanada

The Saccharomyces cerevisiae silencing information regulator(SIR)complex contains up to four proteins,namely Sir1,Sir2,Sir3,and *** Sir2 encodes a NAD-dependent histone deacetylase,other SIR proteins mainly function as structural and scaffold components through physical interaction with various *** SIR complex displays different conformation and composition,including Sir2 homotrimer,Sir1-4 heterotetramer,Sir2-4 heterotrimer,and their derivatives,which recycle and relocate to different chromosomal *** activities of the SIR complex are transcriptional silencing through chromosomal remodeling and modulation of DNA double-strand-break repair *** activities allow the SIR complex to be involved in mating-type maintenance and switching,telomere and subtelomere gene silencing,promotion of nonhomologous end joining,and inhibition of homologous recombination,as well as control of cell *** review explores the potential link between epigenetic regulation and DNA damage response conferred by the SIR complex under various conditions aiming at understanding its roles in balancing cell survival and genomic stability in response to internal and environmental *** core activities of the SIR complex are highly conserved in eukaryotes from yeast to humans,knowledge obtained in the yeast may apply to mammalian Sirtuin homologs and related diseases.

关键词： chromatin remodeling DNA-damage response SiR complex transcriptional silencing yeast

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

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World Journal of Gastroenterology 2024年第10期30卷 1280-1286页

作者： Valerie josephine Dirjayanto Jessica Audrey Daniel Martin Simadibrata Faculty of Medicine Universitas IndonesiaJakarta Pusat 10430DKI JakartaIndonesia Division of Gastroenterology and Hepatology Mayo ClinicRochesterMinnesota 55905United States Nuffield Department of Population Health University of OxfordOxford OX37LFUnited Kingdom

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(***)for the rescue therapy against Helicobacter pylori(***),a pathogen responsible for peptic ulcers and gastric *** is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by *** to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid *** with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for *** studies suggested that *** plays a role in stabilizing the gut barrier which improves *** eradication *** an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical ***,*** comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue ***,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

关键词： Vonoprazan Saccharomyces boulardii Helicobacter pylori Rescue therapy Eradication rate

Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 308-325页

作者： Adilson Fonseca Teixeira Yanhong Wang josephine Iaria Peter ten Dijke Hong-Jian Zhu Department of Surgery(The Royal Melbourne Hospital) The University of MelbourneParkvilleVICAustralia Huagene Institute Kecheng Science and Technology ParkPukou DistrictNanjingJiangsuChina Department of Cell and Chemical Biology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands

Metastasis is the leading cause of cancer-related *** growth factor beta(TGF-β)signaling drives metastasis and is strongly enhanced during cancer ***,the use of on-target TGF-βsignaling inhibitors in the treatment of cancer patients remains unsuccessful,highlighting a gap in the understanding of TGF-βbiology that limits the establishment of efficient anti-metastatic ***,we show that TGF-βsignaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle(sEV)*** sEV’s unique role,TGF-βsignaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β.Further,genetic disruption of sEV secretion in highlymetastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-βsignaling to nearly-normal ***,TGF-βsignaling activity in non-invasive breast cancer cells is inherently low,but can be amplified by sEVs,enabling invasion and metastasis of poorly-metastatic breast cancer *** the translational potential of inhibiting sEV trafficking in advanced breast cancers,treatment with dimethyl amiloride(DMA)decreases sEV secretion,TGF-βsignaling activity,and breast cancer progression in *** both the sEV trafficking and TGF-βsignaling by combining DMA and SB431542 at suboptimal doses potentiated this effect,normalizing the TGF-βsignaling in primary tumors to potently reduce circulating tumor cells,metastasis,and tumor ***,this study establishes sEVs as critical elements in TGF-βbiology,demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-βsignaling levels in breast cancer cells.

关键词： metastasis doses invasion

A simulation study on spatial and time resolution for a cost-effective positron emission particle tracking system

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Particuology 2024年第5期88卷 312-322页

作者： josephine Oppotsch Matthias Steinke Miriam Fritsch Fritz-Herbert Heinsius Thomas Held Nikoline Hilse Viktor Scherer Ulrich Wiedner Ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany Ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

This work is the second part of a simulation study investigating the processing of densely packed and moving granular assemblies by positron emission particle tracking (PEPT).Since medical positron emission tomography (PET) scanners commonly used for PEPT are very expensive,a PET-like detector system based on cost-effective organic plastic scintillator bars is being developed and tested for its *** this context,the spatial resolution of a resting positron source,a source moving on a freely designed model path,and a particle motion given by a discrete element method (DEM) simulation is studied using Monte Carlo simulations and the software toolkit *** not only extended the simulation and reconstruction to a moving source but also significantly improved the spatial resolution compared to previous work by adding oversampling and iteration to the reconstruction ***,in the case of a source following a trajectory developed from DEM simulations,a very good resolution of about 1 mm in all three directions and an average 3D deviation between simulated and reconstructed events of 2.3 mm could be ***,the resolution for realistic particle motion within the generic grate system (which is the test rig for further experimental studies) is well below the smallest particle *** simulation of the dependence of the reconstruction accuracy on tracer particle location revealed a nearly constant efficiency within the entire detector system,which demonstrates that boundary effects can be neglected.

关键词： Positron emission particle tracking Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

Prevalence and intensity of urinary schistosomiasis and soil-transmitted helminths among women of reproductive age in Mwaluphamba,Kwale

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Asian Pacific Journal of Tropical Medicine 2024年第2期17卷 71-83页

作者： Samuel M.Ngui Joseph M.Mwangangi Joachim Richter josephine W.Ngunjiri Department of Biological Sciences University of EmbuKenya Medical Entomology Kenya Medical Research Institute(KEMRI)Center for Geographic Medicine Research Coast KilifiKenya Institute of International Health Global Health CenterCharitéUniversity MedicineBerlinCorporate Member of Free University and Humboldt University and Berlin Institute of HealthBerlinGermany Swiss Tropical and Public Health Institute BaselSwitzerland Tropical and Infectious Diseases Department of Biological sciencesUniversity of EmbuKenya

Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,***:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba *** specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine ***’sociodemographic details were obtained using a standardized ***:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 *** patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,*** without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a ***,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary *** bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.

关键词： Urinary schistosomiasis Prevalence Soiltransmitted helminths Mwaluphamba

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： Dorothy Liu Mark M Youssef josephine A Grace Marie Sinclair Department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of Medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant *** immunosuppression has been shown to contribute to post-transplant malignancy(PTM)*** is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of *** inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour *** transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this ***,there is limited clinical data on this subject in both LT and other solid organ transplant *** To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ *** A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August *** terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the *** lists of retrieved articles were also reviewed to identify any additional *** duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in ***-text articles were assessed for eligibility based on pre-specified inclusion and exclusion *** A total of 6 studies were included in this *** studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol us

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus Mycophenolate

A simulation study for a cost-effective PET-like detector system intended to track particles in granular assemblies

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Particuology 2024年第1期84卷 117-125页

作者： josephine Oppotsch Antonios Athanassiadis Miriam Fritsch Fritz-Herbert Heinsius Thomas Held Nikoline Hilse Viktor Scherer Matthias Steinke Ulrich Wiedner Ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany Ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

Since many industrial applications rely on the processing of densely packed and moving granular ma-terial,obtaining bulk internal information on the particle movement inside the reactors is of great *** information can be delivered by Positron Emission Particle Tracking(PEPT).By marking pellets with a positron-emitting radioisotope,the position of these tracer particles can be determined via the time-of-flight differences of the emitted gamma-ray *** current paper proposes a PET-like detector system based on cost-effective organic plastic scintillators instead of the more common but expensive inorganic *** system is currently under construction and was tested for its resolution and efficiency in this simulation *** Monte Carlo simulations and the software toolkit Geant4,three different geometries(an empty glass box,a generic grate system,and a cubic box of 1 m3 completely filled with pellets)were investigated,leading to a spatial resolution in the millimeter range and an efficiency,defined as the ratio of reconstructed decay locations to simulated decays,of 2.7%,1.4%,and 0.3%.

关键词： Positron emission particle tracking Geant4 Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

Ananda Sukarlan's Rapsodia Nusantara No.3(2009) and the Romantic Virtuosity Connection

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Ananda Sukarlan's Rapsodia Nusantara No.3(2009) and the Roma...

作者：赵思平（josephine Aurelia）成都大学

学位级别：硕士

备受尊敬的印尼作曲家安南达·苏卡兰(Ananda Sukarlan),通过将本土民歌和传统音乐元素融合进多样化的作品中,大大丰富了印尼音乐体系。这些作品包括声乐和器乐两大类。在他众多值得注意的音乐作品中,《瓦普索迪亚·努桑塔拉第三号》(Ra... 详细信息

备受尊敬的印尼作曲家安南达·苏卡兰(Ananda Sukarlan),通过将本土民歌和传统音乐元素融合进多样化的作品中,大大丰富了印尼音乐体系。这些作品包括声乐和器乐两大类。在他众多值得注意的音乐作品中,《瓦普索迪亚·努桑塔拉第三号》(Rapsodia Nusantara No.3)是一部技巧性极高的独奏钢琴杰作。由于之前的文献主要是对《瓦普索迪亚·努桑塔拉》整部作品的整体风格研究,笔者将本文研究的重点放在了探讨这一特定作品与浪漫技巧性主题之间的关系上面。《瓦普索迪亚·努桑塔拉第三号》与浪漫作品之间有大量相似之处。本文探究苏卡兰如何与浪漫时期作品紧密相关,其最终目的是提升音乐表达和演奏技巧。将苏卡兰的作品与浪漫时期作品比较研究是为了阐明其风格上的联系,对演奏者在演奏技巧、音乐表达和整体艺术性上产生积极影响。笔者将对乐谱,特别是技巧性元素方面,进行细致分析。该分析将《瓦普索迪亚·努桑塔拉第三号》与浪漫主义作曲家的作品并列比较。研究发现苏卡兰的作品中技巧性元素具有重要意义,并为钢琴家深入挖掘这部作品的复杂性并以细腻的方式诠释它提供重要的视角。探索本作品与浪漫技巧性的联系,不仅有助于钢琴家深入理解作品,还能激发他们探索印尼音乐体系的更兴趣。最终,这项研究将对当代印尼古典音乐在全球的重要性作出贡献,将展示苏卡兰作品的丰富性和创新性,同时将为演奏者提供演奏技术和表现力上的的重要指导。

关键词：安南达·苏卡兰瓦普索迪亚·努桑塔拉第三号浪漫时期作品主题变奏

Complement factor H in molecular regulation of angiogenesis

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Medical Review 2024年第5期4卷 452-466页

作者： Jiang Li Kaili Wang Maria N.Starodubtseva Eldar Nadyrov Carolyn M.Kapron josephine Hoh Ju Liu Laboratory of Translational Medicine in Microvascular Regulation Institute of Microvascular MedicineMedical Research CenterThe First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJinanShandong Province250014China Shandong Provincial Key Medical and Health Laboratory of Translational Medicine in Microvascular Aging JinanShandong ProvinceChina Medical Research Center Shandong Provincial Qianfoshan HospitalShandong UniversityJinanShandong Province 250014China Gomel State Medical University GomelBelarus Institute of Radiobiology of NAS of Belarus GomelBelarus Department of Biology Trent UniversityPeterboroughONCanada Department of Ophthalmology Yale School of MedicineNew HavenCTUSA

Angiogenesis,the process of formation of new capillaries from existing blood vessels,is required for multiple physiological and pathological *** factorH(CFH)is a plasma protein that inhibits the alternative pathway of the complement *** of CFH enhances the alternative pathway and increases complement activation fragments with pro-angiogenic capacity,including complement 3a,complement 5a,and membrane attack *** protein contains binding sites for C-reactive protein,malondialdehyde,and endothelial heparan *** of CFH prevents its interaction with these molecules and initiates pro-angiogenic *** in the CFH gene have been found in patients with age-related macular degeneration characterized by choroidal *** Cfh-deficient mice show an increase in angiogenesis,which is decreased by administration of recombinant CFH pro*** this review,we summarize the molecular mechanisms of the anti-angiogenic effects of CFH and the regulatory mechanisms of CFH *** therapeutic potential of recombinant CFH protein in angiogenesisrelated diseases has also been discussed.

关键词： complement factor H angiogenesis mechanical properties therapeutic target