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Methyltransferase-like 3(METTL3)inhibition potentiates anti-tumor immunity:a novel strategy for improving anti-PD1 therapy

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Signal Transduction and Targeted Therapy 2024年第1期9卷 10-11页

作者： Anna Brichkina roman Suezov Magdalena huber Institute of Systems Immunology Member of the German Center for Lung Research(DZL)Philipps University of Marburg35043 MarburgGermany

In a recent article published in Cancer Discovery,Guirguis et *** that enzymatic inhibitors of the m6 A methyltransferase METTL3 induced a formation of immunostimulatory doublestranded mrNAs(dsrNAs)in cancer cells,which triggered a profound tumor-cell-intrinsic interferon response leading to an enhanced antigen presentation and thereby increased killing of tumor cells by cytotoxic CD8+*** inhibition of METTL3 synergized with anti-PD1 immunotherapy,highlighting its potential for improving cancer treatment.

关键词： PD1 immunity

rapid and accurate alpha-thalassemia-screening using light cycler technology

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Rapid and accurate alpha-thalassemia-screening using light c...

Pathogenic and therapeutic role of exosomes in neurodegenerative disorders

中华医学会第八次全国检验医学学术会议暨中华医学会检验分会成立30周年庆典大会

作者： S.Brunner-Agten r.Herklotz L.Bernasconi B.M.Stadler a.r.huber Centre of Laboratory Medicine Cantonal Hospital Aarau(KSA)Switzerland Institut of Immunology Inselspital BernUniversity of BernSwitzerland

α-Thalassemia is one of the most common genetic disorders with a world wide prevalence of 3-4%.It is mainly the result of deletions on chromosome 16 due to crossing-overs between the two highly homologous and closely linked genes(α1-andα2-gene) in theα-*** loss of oneα-gene leads toα-Thalassemia, whereas the loss of bothα-genes results inα0-Tha-

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Neural regeneration research 2024年第1期19卷 75-79页

作者： Christa C.huber Hongmin Wang Division of Basic Biomedical Sciences Sanford School of MedicineUniversity of South DakotaVermillionSDUSA

Neurodegenerative disorders affect millions of people worldwide,and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming *** therapies exist to aid in symptomatic relief,effective treatments that can stop or reve rse the progress of each neurodegenerative disease are ***,research on the role of extracellular vesicles as disease markers and therapeutics has been intensively ***,30-150 nm in diameter,are one type of extracellular vesicles facilitating cell-to-cell *** are thought to play a role in disease propagation in a variety of neurodegenerative diseases,such as Alzheimer's disease,Parkinson s disease,and amyotrophic lateral ***,the exosomes derived from the patients are an invaluable source of disease *** the other hand,exosomes,especially those derived from stem cells,could serve as a therapeutic for these disorders,as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological *** review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative *** also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic ***,this review concludes with outstanding questions that remain to be addressed in exosomal research.

关键词： aging Alzheimer's disease biomarker drug exosome extracellular vesicle neurodegenerative disease Parkinson's disease therapy

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

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Genes & Diseases 2024年第4期11卷 381-399页

作者： Ming Shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Department of Chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational Biology St.Jude Children's Research HospitalMemphisTN 38105USA Center for Proteomics and Metabolomics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Structural Biology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental Neurobiology St.Jude Children's Research HospitalMemphisTN 38105USA

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in ***,it remains unclear whether CYP3A5 directly influences cancer *** this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal ***-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of ***,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling ***3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic *** together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

关键词： Cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim Böttrich Pascal Bauer Vincent Gröβer Magdalena huber Hartmann raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer robert ringseis Klaus Eder Karsten Krüger Christopher Weyh Department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(Or)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly regulatory T cells Subclinical atherosclerosis

Analysis and Optimization of Operational and Pollutant Attributes of Diesel Engine with CNT-Infused Orange Peel Biodiesel-Diesel Blend Fuel

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Journal of Thermal Science 2024年第2期33卷 761-778页

作者： ranjeet rAI r.r.SAHOO Mechanical Engineering Department GLA UniversityMathura281406India Mechanical Engineering Department IIT(BHU)Varanasi221005India

The current study is performed to find sustainable solutions for the future of transportation and environmental *** conventional methods and experimental design table(L16 Orthogonal Array)techniques have been employed to examine and optimize a diesel-powered engine's operational and pollutant *** L16 Orthogonal Array is obtained through Taguchi's experimental design approach using Minitab 16 *** experimental design incorporated three control variables,namely engine speed,fuel type,and engine load,each with four *** operational parameters,namely brake thermal efficiency(BTE)and brake specific fuel consumption(BSFC),as well as the emission characteristics,including hydrocarbon(HC),carbon monoxide(CO),nitrogen oxide(NO),and smoke emissions,were acquired using the L16 orthogonal array(OA) and subsequently *** utilization of methodologies such as signal-to-noise(S/N) ratio and grey analysis was employed to determine the optimal operational state of the engine to achieve maximum performance while minimizing *** engine's ideal state of operation,in terms of BTE and BSFC,was determined to be at 75% engine load,1000 r/min engine speed,and using 10^(-4)(in vol) carbon nanotube incorporated 20% orange peel biodiesel(OPB20CNT100) blended fuel(A3-B1-C4).The study indicated that engine load significantly influenced BTE and BSFC,with 84.05% and 87.79% contribution factors,*** 25% engine load,1000 r/min,and OPB20CNT100 fuel(A1-B1-C4) CO,smoke,NO,and HC emissions were the *** load affects emissions the *** BSFC increased 3.10% and NO emissions 1.77%.BTE,CO,smoke,and HC emissions decreased by 1.9%,12.29%,47.05%,and 47.22%,respectively,at optimal operating conditions concerning diesel *** study shows that Taguchi-Grey's experimental design optimizes diesel engine operational and pollutant *** outcomes revealed that orange peel biodiesel infused with CNT can replace diesel fuel in a

关键词： Taguchi-Grey method OPB20CNT100 transesterification S/N ratio GrG HC CO and NO

Kinematic analysis of flexible bipedal robotic systems

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Applied Mathematics and Mechanics(English Edition) 2024年第5期45卷 795-818页

作者： r.FAZEL A.M.SHAFEI S.r.NEKOO Department of Mechanical Engineering Shahid Bahonar University of KermanKerman ***Iran Departamento de Ingenieria de Sistemas y Automatica Escuela Técnica Superior de IngenieriaUniversidad de SevillaSeville 41092Spain

In spite of its intrinsic complexities,the passive gait of bipedal robots on a sloping ramp is a subject of interest for numerous *** distinguishes the present research from similar works is the consideration of flexibility in the constituent links of this type of robotic *** is not a far-fetched assumption because in the transient(impact)phase,due to the impulsive forces which are applied to the system,the likelihood of exciting the vibration modes increases ***,the human leg bones that are involved in walking are supported by viscoelastic muscles and ***,for achieving more exact results,it is essential to model the robot links with viscoelastic *** this end,the Gibbs-Appell formulation and Newton's kinematic impact law are used to derive the most general form of the system's dynamic equations in the swing and transient phases of *** most important issue in the passive walking motion of bipedal robots is the determination of the initial robot configuration with which the system could accomplish a periodic and stable gait solely under the effect of gravitational *** extremely unstable nature of the system studied in this paper and the vibrations caused by the impulsive forces induced by the impact of robot feet with the inclined surface are some of the very serious challenges encountered for achieving the above-mentioned *** overcome such challenges,an innovative method that uses a combination of the linearized equations of motion in the swing phase and the algebraic motion equations in the transition phase is presented in this paper to obtain an eigenvalue *** solving this problem,the suitable initial conditions that are necessary for the passive gait of this bipedal robot on a sloping surface are *** effects of the characteristic parameters of elastic links including the modulus of elasticity and the Kelvin-Voigt coefficient on the walking stability of this type of

关键词： bipedal robot flexible link swing phase transient phase eigenvalue problem Kelvin-Voigt coefficient

Holographic dark energy in non-conserved gravity theory

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Communications in Theoretical Physics 2024年第4期76卷 126-133页

作者： H r Fazlollahi Institute of Gravitation and Cosmology Peoples Friendship University of Russia(RUDN University)6 Miklukho-Maklaya StMoscow117198Russia

recently, reconsidering the rastall idea T_(μ;νν)^(v)=α_(,μ) through relativistic thermodynamics gives a new form for the scalar field α which led us to construct modern modified theory of gravity debugged ‘non-conserved gravity theory’ Fazlollahi 2023 Euro. Phys. J. C 83 923. This theory unlike other modified theories of gravity cannot directly explain the current acceleration expansion in the absence of the cosmological constant and or existence of other forms of dark energy. Hence, in this study we have reinvestigated holographic dark energy Ρ_(X)~H^(2) in the non-conserved theory of gravity. In this context, the density and pressure of dark energy depend on the non-conserved term and density of the dust matter field. As shown, due to non-conservation effects on large-scale structures, unlike the original holographic model, our model onsets an acceleration epoch for the current Universe satisfies observations. Moreover, the interaction and viscous scenarios are studied for this model.

关键词： non-conserved gravity covariant form of thermodynamics holographic dark energy

Pile foundation in alternate layered liquefiable and non-liquefiable soil deposits subjected to earthquake loading

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 359-376页

作者： Praveen Huded M Suresh r Dash LEA Associates South East Asia Pvt.Ltd. New Delhi 110044India Indian Institute of Technology Bhubaneswar Khurda 752050India

Pile foundations are still the preferred foundation system for high-rise structures in earthquake-prone *** foundations have experienced failures in past earthquakes due to *** on pile foundations in liquefiable soils has primarily focused on the pile foundation behavior in two or three-layered soil ***,in natural occurrence,it may occur in alternative layers of liquefiable and non-liquefiable ***,the experimental and/or numerical studies on the layered effect on pile foundations have not been widely addressed in the *** of the design codes across the world do not explicitly mention the effect of sandwiched non-liquefiable soil layers on the pile *** the present study,the behavior of an end-bearing pile in layered liquefiable and non-liquefiable soil deposit is studied *** study found that the kinematic bending moment is higher and governs the design when the effect of the sandwiched non-liquefied layer is considered in the analysis as opposed to when its effect is ***,ignoring the effect of the sandwiched non-liquefied layer in a liquefiable soil deposit might be a nonconservative design approach.

关键词： pile foundation liquefaction alternately layered soil fixity effect layered effect