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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang Lingli Wang Yibo Ding renxian Tang Xiucheng Pan Kuiyang Zheng Luc J.Wvan der Laan Qiuwei Pan Wenshi Wang Department of Pathogen Biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SArS-CoV-2 *** selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634r).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

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Flexible neural probes:a review of the current advantages,drawbacks,and future demands

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 153-167页

作者： Sara PIMENTA Joao r.FrEITAS JoséH.COrrEIA CMEMS-UMinho University of MinhoGuimarães4800-058Portugal LABBELS-Associate Laboratory Braga/GuimarãesPortugal

Brain diseases affect millions of people and have a huge social and economic *** use of neural probes for studies in animals has been the main approach to increasing knowledge about neural network ***,neuroscientists are trying to develop new and more effective therapeutic approaches to treating neurological *** implementation of neural probes with multifunctionalities(electrical,optical,and fluidic interactions)has been increasing in the last few years,leading to the creation of devices with high temporal and spatial *** the applicability of,and elements integrated into,neural probes has also led to the necessity to create flexible interfaces,reducing neural tissue damage during probe implantation and increasing the quality of neural acquisition *** this paper,we review the fabrication,characterization,and validation of several types of flexible neural probes,exploring the main advantages and drawbacks of these ***,future developments and applications are ***,this review aims to present the currently available flexible devices and future appropriate avenues for development as possible guidance for future engineered devices.

关键词： Brain knowledge Flexible interface Multifunctional probe

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results of the Second Life Metabolism Travel Awards 2024

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Life Metabolism 2024年第3期3卷 1-2页

作者： John r.Speakman Shenzhen Key Laboratory of Metabolic Health Center for Energy Metabolism and ReproductionShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Institute of Biological and Environmental Sciences University of AberdeenAberdeenAB242TZScotlandUnited Kingdom

This year is the second year of the Life Metabolism Travel Prize Awards for PhD students and *** three 700 US$awards are generously sponsored by Sable Systems-Promethion(China)who manufacture metabolic *** I announce the winners and their interesting projects,I will just reiterate how the judging of the awards *** first remove anything from the submission that would identify the sex,affiliation,or ethnicity of the applicant.

关键词： remove Travel Awards

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Evaluation of Some Treatment Options Inlate and Neglected Hip Fractures Using the Modified Harris Hip Score

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Open Journal of Orthopedics 2024年第6期14卷 259-269页

作者： Shaphat Shuaibu Ibrahim Abubakar Musa Olaoluwa Moses Shodipo Emuan timothy Zailani Buhari Stephen Yusuf Mienda Isa Department of Orthopaedics Abubakar Tafawa-Balewa University Teaching Hospital (ATBUTH) Bauchi Nigeria Orthopaedic Unit Department of Surgery FMC Bida Nigeria

Background: The choice of the appropriate operative intervention in patients with late and neglected hip fracture continuous to be a huge dilemma for orthopedic surgeons. Purpose: To evaluate the satisfaction or otherwise of some treatment options using the modified Harris-hip score (HHS) in resource poor setting. Materials and Methods: A retrospective cross-sectional study conducted at ATBUTH, Bauchi. Data of 60 patients over the age of 18 years with hip fractures (femoral neck, intertrochanteric and sub trochanteric fractures) who had operative intervention between 1st September 2019 and 31st August 2020 with cannulated screws, Proximal femur lock compression plate (PFLCP), cementlessor cemented bipolar hemiarthroplasty (BHA). results: The mean age of studied patients was 65.7 ± 16.1 years, with age ranging from 19 - 101 years. M:F ratio was 1.2:1 across all age groups and 1:1.4 amongst those >60 years. 51 patients (85%) presented > 1 week after injury with 24 patients (40%) sustaining hip fractures from low energy trivial indoor fall and 28 patients (46.7%) mostly younger sustaining fractures from high energy motor vehicular accident (MVA). The prevalence rate for femoral neck, intertrochanteric and subtrochanteric fractures were 32 (53.3%), 17 (28.3%) and 11 (18.3%) respectively. From the data retrieved, 21patients (35.0%), 17 patients (28.3%), 20 patients (33.3%) and 2 patients (3.3%) had PFLCP, cemented BHA, cementless BHA and cannulated screw fixation respectively. Most (66.7%) of those who had PFLCP achieved satisfactory radiologic union and there was also 94.1% and 85% satisfactory outcome rate amongst the patients with cemented BHA and cementless BHA respectively. Irrespective of the operative intervention method at 1 year follow-up, there was a statistically significant improvement in post-operative HHS (P value 0.02), with 83.4% having good to excellent results. Conclusion: There is highrate of late and neglected hip fracture in our environment. Satisfac

关键词： Hip Fracture Late and Neglected BHA PFLCP Cannulatedscrew Outcome Measures HHS

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Excellent photoluminescence and electrochemical properties of Sm^(3+) doped Ca_(2)MgSi_(2)O_(7) nanophosphor:Display and electrochemical sensor applications

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Journal of rare Earths 2024年第6期42卷 1046-1055,I0002页

作者： r.B.Basavaraj K.Sureshkumar D.P.Aarti M.B.Madhusudana reddy G.Nagaraju T.ramakrishnappa G.r.Navyashree K.r.Venkatesha Babu K.S.Hemalatha Department of Physics BMS Institute of Technology and ManagementBangalore560064India Department of Chemistry BMS Institute of Technology and ManagementBangalore560064India Department of Chemistry School of Applied SciencesREVA UniversityBangalore560064India Energy Materials researchLaboratory Department of ChemistrySiddaganga Institute of TechnologyTumakuru57203KarnatakaIndia School of Physical Sciences REVA UniversityBangalore560057Indi Department of Physics Govt.Science CollegeBengaluru560001India Department of Physics Maharani Science College for WomenMaharani Cluster UniversityBengaluru560001India

A series of orange-red light emitting Ca_(2)MgSi_(2)O_(7):Sm^(3+)nanopowders were fabricated via low-cost ecofriendly green combustion technique using Aloe vera gel as *** phase purity of the samples were confirmed by the powder X-ray diffraction(PXrD)*** single-phase tetragonal structure is observed from the PXrD results with no additional impurity *** band gap energy of the fabricated powders was estimated by diffuse reflectance spectra(DrS)and is found to be in the range of 4.01-5.98 eV.A high resolution scanning electron microscope(SEM)was used to study the morphological behaviour of the ***-like structures are observed from the SEM *** particle size was evaluated by transmission electron microscopy(TEM)and is found to be~50 *** interplanar distance is found to be 0.53 *** properties were systematically studied in *** phosphors are successfully excited at 403 nm NUV light,producing reddish-orange characteristic *** emission peaks are centered at 558(^(4)G_(5/2)→^(6)H_(5/2)),607(^(4)G_(5/2)→^(6)H_(7/2))and 645 nm(^(4)G_(5/2)→^(6)H_(9/2)),*** the observed peaks the red emanation(^(4)G_(5/2)→^(6)H_(7/2))is stronger than the orange emission(^(4)G_(5/2)→^(6)H_(5/2))in the current *** photoluminescent concentration quenching is noticed above 5 mol%Sm^(3+)ion doping *** dipole-dipole interaction resulting in cross relaxation is found to be the principal cause of concentration quenching *** color features such as Commission Internationale de I’Eclairage(CIE)and correlated color temperature(CCT)were studied in *** optimized chromaticity coordinates were estimated to be(0.6363,0.3632),which fall in the reddish-orange *** average CCT value obtained is 3362 *** average color purity is found to be~82%.Sm^(3+)incorporated Ca_(2)MgSi_(2)O_(7) samples are possible contender for single white light generation commercial candidates owing to

关键词： Green combustion Photoluminescence Orange-red emission Color purity Sensors rare earths

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A Collocation Technique via Pell-Lucas Polynomials to Solve Fractional Differential EquationModel for HIV/AIDS with Treatment Compartment

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Computer Modeling in Engineering & Sciences 2024年第10期141卷 281-310页

作者： Gamze Yıldırım Suayip Yüzbası Department of Mathematics Faculty of ScienceAkdeniz UniversityAntalya07058Turkey Department of Mathematics Faculty of Basic ScienceGebze Technical UniversityKocaeli41400Turkey Department of Mathematics Faculty of ScienceBartın UniversityBartın74100Turkey

In this study,a numerical method based on the Pell-Lucas polynomials(PLPs)is developed to solve the fractional order HIV/AIDS epidemic model with a treatment *** HIV/AIDS mathematical model with a treatment compartment is divided into five classes,namely,susceptible patients(S),HIV-positive individuals(I),individuals with full-blown AIDS but not receiving ArV treatment(A),individuals being treated(T),and individuals who have changed their sexual habits sufficiently(r).According to the method,by utilizing the PLPs and the collocation points,we convert the fractional order HIV/AIDS epidemic model with a treatment compartment into a nonlinear system of the algebraic ***,the error analysis is presented for the Pell-Lucas approximation *** aim of this study is to observe the behavior of five populations after 200 days when drug treatment is applied to HIV-infectious and full-blown AIDS *** demonstrate the usefulness of this method,the applications are made on the numerical example with the help of *** addition,four cases of the fractional order derivative(p=1,p=0.95,p=0.9,p=0.85)are examined in the range[0,200].Owing to applications,we figured out that the outcomes have quite decent ***,we understand that the errors decrease when the value of N *** figures in this study are created in *** outcomes indicate that the presented method is reasonably sufficient and correct.

关键词： Collocation method fractional differential equations HIV/AIDS epidemic model Pell-Lucas polynomials

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Doubled haploid technology and synthetic apomixis:recent advances and applications in future crop breeding

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Molecular Plant 2024年第7期17卷 1005-1018页

作者： Yanzhi Qu Alisdair r.Fernie Jie Liu Jianbing Yan National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan 430070China Hubei Hongshan Laboratory Wuhan 430070China Department of Molecular Physiology Max-Planck-Institute of Molecular Plant Physiology14476 Potsdam-GolmGermany Center of Plant Systems Biology and Biotechnology 4000 PlovdivBulgaria azhouwan National Laboratory Sanya 572024China

Doubled haploid(DH)technology and synthetic apomixis approaches can considerably shorten breeding cycles and enhance breeding *** with traditional breeding methods,DH technology offers the advantage of rapidly generating inbred lines,while synthetic apomixis can effectively fix hybrid *** this review,we focus on(i)recent advances in identifying and characterizing genes responsible for haploid induction(Hl),(ii)the molecular mechanisms of Hl,(ili)spontaneous haploid genome doubling,and(iv)crop synthetic *** also discuss the challenges and potential solutions for future crop breeding programs utilizing DH technology and synthetic ***,we provide our perspectives about how to integrate DH and synthetic apomixis for precision breeding and de novo domestication.

关键词： maize doubled haploid technology haploid induction synthetic apomixis precision breeding

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Stable diffusion gradients in microfluidic conduits bounded by fluid walls

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Microsystems & Nanoengineering 2024年第3期10卷 357-367页

作者： Federico Nebuloni Cyril deroy Peter r.Cook Edmond J.Walsh Department of Engineering Science Osney Thermo-Fluids InstituteUniversity of OxfordOxford OX20ESUK Sir William Dunn School of Pathology University of OxfordOxford OX13REUK

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical *** assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in *** microfluidic devices are fabricated using solid plastics that prevent direct access to responding ***-walled microfluidics allows the manufacture of circuits on standard Petri dishes in seconds,coupled to simple operating methods;cell-culture medium sitting in a standard dish is confined to circuits by fluid walls made of an immiscible *** develop and experimentally validate an analytical model of diffusion between two or more aqueous streams flowing at different rates into a fluid-walled conduit with the cross-section of a circular *** solid walls,fluid walls morph during flows as pressures fall,with wall shape changing down the *** model is validated experimentally for Fourier numbersrescein diffusing between laminar *** enables a priori prediction of concentration gradients throughout a conduit,so allowing rapid circuit design as well as providing bioscientists with an accurate way of predicting local concentrations of bioactive molecules around responsive and nonresponsive cells.

关键词： walls diffusion attractive

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Nonlinear corrections for the nuclear gluon distribution in eA processes

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Chinese Physics C 2024年第3期48卷 52-64页

作者： G.r.Boroun B.rezaei F.Abdi Department of Physics Razi UniversityKermanshah 67149Iran.

An analytical study with respect to the nonlinear corrections for the nuclear gluon distribution function in the next-to-leading order approximation at small x is *** consider the nonlinear corrections to the nuclear gluon distribution functions at low values of x and Q^(2) using the parametrization F_(2)(x,Q^(2))and the nuclear modification factors obtained from the Khanpour-Soleymaninia-Atashbar-Spiesberger-Guzey *** CT18 gluon distribution is used for the baseline proton gluon density at Q^(2)_(0)=*** discuss the behavior of the gluon densities in the next-to-leading order and the next-to-next-to-leading order approximations at the initial scale Q^(2)_(0),as well as the modifications due to the nonlinear *** find that the QCD nonlinear corrections are more significant for the next-to-leading order accuracy than the next-to-next-to-leading order for light and heavy *** results of the nonlinear GLr-MQ evolution equation are similar to those obtained with the rausch-Guzey-Klasen gluon upward and downward evolutions within the *** magnitude of the gluon distribution with the nonlinear corrections increases with a decrease in x and an increase in atomic number A.

关键词： gluon distribution nonlinear corrections light and heavy nuclei low x physics

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Falcon Optimization Algorithm-Based Energy Efficient Communication Protocol for Cluster-Based Vehicular Networks

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Computers, Materials & Continua 2024年第3期78卷 4243-4262页

作者： Youseef Alotaibi B.rajasekar r.Jayalakshmi Surendran rajendran Department of Software Engineering College of ComputingUmm Al-Qura UniversityMakkah21955Saudi Arabia Department of Electronics and Communication Engineering Sathyabama Institute of Science and TechnologyChennai600119India Department of Computer Science and Engineering Panimalar Engineering CollegeChennai600123India Department of Computer Science and Engineering Saveetha School of EngineeringSaveetha Institute of Medical and Technical ScienceChennai602105India

rapid development in Information Technology(IT)has allowed several novel application regions like large outdoor vehicular networks for Vehicle-to-Vehicle(V2V)*** networks give a safe and more effective driving experience by presenting time-sensitive and location-aware *** communication occurs directly between V2V and Base Station(BS)units such as the road Side Unit(rSU),named as a Vehicle to Infrastructure(V2I).However,the frequent topology alterations in VANETs generate several problems with data transmission as the vehicle velocity differs with ***,the scheme of an effectual routing protocol for reliable and stable communications is *** research demonstrates that clustering is an intelligent method for effectual routing in a mobile ***,this article presents a Falcon Optimization Algorithm-based Energy Efficient Communication Protocol for Cluster-based routing(FOA-EECPCr)technique in *** FOA-EECPCr technique intends to group the vehicles and determine the shortest route in the *** accomplish this,the FOA-EECPCr technique initially clusters the vehicles using FOA with fitness functions comprising energy,distance,and trust *** the routing process,the Sparrow Search Algorithm(SSA)is derived with a fitness function that encompasses two variables,namely,energy and distance.A series of experiments have been conducted to exhibit the enhanced performance of the FOA-EECPCr *** experimental outcomes demonstrate the enhanced performance of the FOA-EECPCr approach over other current methods.

关键词： Vehicular networks communication protocol clustering falcon optimization algorithm routing

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