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mRNA vaccines:a new era in vaccine development

Oncology Research 2024年第10期32卷 1543-1564页

作者： sHUBHRA CHANDRA JENNIFER C.WILsON DAVID good MING Q.WEI school of Pharmacy&Medical sciences Gold Coast campusGriffith UniversityBrisbaneQLD-4222Australia Menzies Health Institute Queensland(MHIQ) Gold Coast CampusGriffith UniversityBrisbaneQLD-4215Australia school of Allied Health Australian Catholic UniversityBrisbaneQLD-4014Australia

The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of *** article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer *** cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune *** vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant *** personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual *** breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in *** mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic *** trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and *** candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,*** successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune *** the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread *** development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer ***,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.

关键词： Cancer immunotherapy Immune checkpoint Preventive&therapeutic vaccine Delivery system mRNA

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Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

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Protein & Cell 2024年第9期15卷 661-685页

作者： sadaf Hasan Nabil Ghani Xiangli Zhao Julia good Amanda Huang Hailey Lynn Wrona Jody Liu Chuan-ju Liu Department of Orthopedic surgery New York University Grossman School of MedicineNew YorkNY 10016United States Department of Medicine Division of Internal MedicineSaint Peter’s University HospitalRutgers UniversityNew BrunswickNJ 08901United States Cornell University IthacaNew YorkNYUnited States Department of Biomedical Engineering University of North Carolina Chapel HillChapel HillNC 27599United States New York University NY 14853United States Department of Cell Biology New York University Grossman School of MedicineNew YorkNY 10016United States Department of Orthopedics&Rehabilitation Yale University School of MedicineNew HavenCT 06510United States

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as *** state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver *** is a glycolytic metabolite and a crucial node in various metabolic ***,its role and molecular mechanism in obesity and associated complications are *** this study,we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain,white adipose tissue inflammation,and metabolic *** identify the target proteins of pyruvate,drug affinity responsive target stability was employed with proteomics,cellular thermal shift assay,and isothermal drug response to detect the interactions between pyruvate and its molecular ***,we identified cytosolic phospholipase A2(cPLA2)as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity,white adipose tissue inflammation,and hepatic steatosis in a cPLA2-dependent *** with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated,confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and ***,our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its ***’s prior clinical use indicates that it can be considered a safe and viable alternative for obesity,whether consumed as a dietary supplement or as part of a regular diet.

关键词： metabolic disease pyruvate cytosolic phospholipase obesity

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Effect of Eu3+,Bi3+,and Li+ doping on luminescent property of GdNbO4

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Journal of Rare Earths 2024年第1期42卷 66-75页

作者： s.W.Wi Y.s.Lee Department of Physics and Integrative Institute of Basic sciences Soongsil University

We investigated the emission properties of Eu3+-doped GdNbO4-based oxide phosphors,aiming at improving the Eu3+emission by codoping of Bi3+and Li+.Eu3+singly doped,Eu3+and Bi3+doubly doped,and Eu3+,Bi3+,and Li+triply doped GdNbO4were prepared using a high-temperature solid-state reaction *** red-orange emissions from Eu3+in the singly doped samples are significantly improved by the codoping of Bi3+,mainly due to the energy transfer from Bi3+to Eu3+.The additional codoping of Li+is found to increase the Eu3+emission *** improvement might be attributed to the increase in the photoluminescent quantum yield originating from larger grain sizes and better crystallinity.A detailed analysis of the X-ray diffraction pattern and the asymmetric ratio estimated from the photoluminescence spectra show that the local lattice environment around Eu3+in GdNbO4does not change significantly with the codoping of Bi3+and Li+.Our results indicate that Li+doping is a promising way to improve the emission properties of rare-earth ion-doped GdNbO4phosphors.

关键词： Eu3+ GdNbO4 Codoping of Li+ Photoluminescence sensitizer Rare earths

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First evidence for chiral wobbling of triaxial nuclei

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Nuclear science and Techniques 2024年第7期35卷 4-7页

作者： s.Frauendorf Department of Physics and Astronomy University of Notre DameNotre DameIN 46556USA

Chirality(Greek“handiness”)is a property of many com-plex *** molecules exist in two forms,one being the mirror image of the *** for our hands,it is impossible to make the images identical by a suitable *** two forms are called left-handed and *** have the same binding energy,because the electro-magnetic interaction,which holds the molecule together,does not change under a *** properties that are insensitive to the geometry are also the *** different geometry is the reason why the left-handed form turns the polarization plane of transmitted light in one direction by some angle while the right-handed form turns it in the oppo-site direction by the same ***,the geometrical differences between the two species may have other *** two species of the carvon molecule shown in Fig.1 taste quite differently.

关键词： turns Chiral mirror

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Tribological behavior of lubricant-impregnated porous polyimide

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Friction 2024年第4期12卷 711-725页

作者： Jinbang LI Ningning ZHOU Janet s.s.WONG school of Mechanical Engineering and Mechanics Ningbo UniversityNingbo 315211China Beijing Key Laboratory of Long-life Technology of Precise Rotation and Transmission Mechanisms Beijing Institute of Control EngineeringBeijing 100029China Department of Mechanical Engineering Imperial College LondonLondon SW72AZUK

Porous materials impregnated with lubricants can be used in conditions where limited lubricant is *** this work,three porous polyimides(PPI)with different densities were ***(PAO)impregnated PPI(iPPI)discs were rubbed against steel and sapphire *** operando observations of the iPPI-sapphire contacts show that oil is released under an applied load,forming a meniscus around *** at the outlet is created at high sliding *** amount of released oil increases with increasing PPI *** moduli,E*,estimated based on the actual contact size show that trapped oil in iPPIs contributes to load *** higher speeds,tribological rehydration of the contact occurs in low density iPPI,with that E*rises with *** high density PPIs,high speeds give a constantly high E*which is limited by the viscoelastic properties of the PPI network and possibly the rate of oil *** of iPPI-steel contacts is governed by the mechanical properties of the PPI,the flow of the lubricant,and the roughness of the PPI *** low-and medium-density(highly porous,high roughness)PPIs,large amount of oil is released,and lubrication is mainly via lubricant restricted in the contact in the pores and possibly tribological *** high density(low porosity)PPI,with lower roughness,hydrodynamic lubrication is achieved which gives the lowest *** results show that polymeric porous materials for effective lubrication require the optimization of its surface roughness,stiffness,oil flow,and oil retentions.

关键词： polyimide porous material friction mechanism polymer limited lubrication

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Enhancing fatigue performance of AZ31 magnesium alloy components fabricated by cold metal transfer-based wire arc directed energy deposition through LPB

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Journal of Magnesium and Alloys 2024年第4期12卷 1638-1662页

作者： shambhu Kumar Manjhi srikanth Bontha A.s.s.Balan Department of Mechanical Engineering National Institute of Technology KarnatakaSurathkalSrinivasanagarMangaloreKarnataka 575025India

Cold Metal Transfer-Based Wire Arc Directed Energy Deposition(CMT-WA-DED)presents a promising avenue for the rapid fabrication of components crucial to automotive,shipbuilding,and aerospace ***,the susceptibility to fatigue of CMT-WA-DED-produced AZ31 Mg alloy components has impeded their widespread adoption for critical load-bearing *** this study,a comprehensive investigation into the fatigue behaviour of WA-DED-fabricated AZ31 Mg alloy has been carried out and compared to commercially available wrought AZ31 *** findings indicate that the as-deposited parts exhibit a lower fatigue life than wrought Mg alloy,primarily due to poor surface finish,tensile residual stress,porosity,and coarse grain microstructure inherent in the WA-DED *** Plasticity Burnishing(LPB)treatment is applied to mitigate these issues,which induce significant plastic deformation on the *** treatment resulted in a remarkable improvement of fatigue life by 42%,accompanied by a reduction in surface roughness,grain refinement and enhancement of compressive residual stress ***,during cyclic deformation,WA-DED specimens exhibited higher plasticity and dislocation density compared to both wrought and WA-DED+LPB specimens.A higher fraction of Low Angle Grain Boundaries(LAGBs)in WA-DED specimens contributed to multiple crack initiation sites and convoluted crack paths,ultimately leading to premature *** contrast,wrought and WA-DED+LPB specimens displayed a higher percentage of High Angle Grain Boundaries(HAGBs),which hindered dislocation movement and resulted in fewer crack initiation sites and less complex crack paths,thereby extending fatigue *** findings underscore the effectiveness of LPB as a post-processing technique to enhance the fatigue performance of WA-DED-fabricated AZ31 Mg alloy *** study highlights the importance of LPB surface treatment on AZ31 Mg components produced by CMT-WA-DED to remove surface d

关键词： Wire arc additive manufacturing AZ31 Mg alloy Low plasticity burnishing Low cycle fatigue test strain amplitude

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Ren-integrable and ren-symmetric integrable systems

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Communications in Theoretical Physics 2024年第3期76卷 62-69页

作者： s Y Lou school of Physical science and Technology Ningbo UniversityNingbo315211China

A new type of symmetry,ren-symmetry,describing anyon physics and corresponding topological physics,is ***-symmetry is a generalization of super-symmetry which is widely applied in super-symmetric physics such as super-symmetric quantum mechanics,super-symmetric gravity,super-symmetric string theory,super-symmetric integrable systems and so *** and Grassmann numbers are,in some sense,dual conceptions,and it turns out that these conceptions coincide for the ren situation,that is,a similar conception of ren-number(R-number)is devised for *** particular,some basic results of the R-number and ren-symmetry are exposed which allow one to derive,in principle,some new types of integrable systems including ren-integrable models and ren-symmetric integrable *** examples of ren-integrable KdV-type systems and ren-symmetric KdV equations are explicitly given.

关键词： symmetries integrable systems anyon physics extended supersymmetry ren-symmetry

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AutoRhythmAI: A Hybrid Machine and Deep Learning Approach for Automated Diagnosis of Arrhythmias

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Computers, Materials & Continua 2024年第2期78卷 2137-2158页

作者： s.Jayanthi s.Prasanna Devi Department of Computer science and Engineering SRM Institute of Science and Technology-Vadapalani CampusChennaiTamil NaduIndia

In healthcare,the persistent challenge of arrhythmias,a leading cause of global mortality,has sparked extensive research into the automation of detection using machine learning(ML)***,traditional ML and AutoML approaches have revealed their limitations,notably regarding feature generalization and automation *** glaring research gap has motivated the development of AutoRhythmAI,an innovative solution that integrates both machine and deep learning to revolutionize the diagnosis of *** approach encompasses two distinct pipelines tailored for binary-class and multi-class arrhythmia detection,effectively bridging the gap between data preprocessing and model *** validate our system,we have rigorously tested AutoRhythmAI using a multimodal dataset,surpassing the accuracy achieved using a single dataset and underscoring the robustness of our *** the first pipeline,we employ signal filtering and ML algorithms for preprocessing,followed by data balancing and split for *** second pipeline is dedicated to feature extraction and classification,utilizing deep learning ***,we introduce the‘RRI-convoluted trans-former model’as a novel addition for binary-class *** ensemble-based approach then amalgamates all models,considering their respective weights,resulting in an optimal model *** our study,the VGGRes Model achieved impressive results in multi-class arrhythmia detection,with an accuracy of 97.39%and firm performance in precision(82.13%),recall(31.91%),and F1-score(82.61%).In the binary-class task,the proposed model achieved an outstanding accuracy of 96.60%.These results highlight the effectiveness of our approach in improving arrhythmia detection,with notably high accuracy and well-balanced performance metrics.

关键词： Automated machine learning neural networks deep learning arrhythmias

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Machine learning-enhanced Monte Carlo and subset simulations for advanced risk assessment in transportation infrastructure

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Journal of Mountain science 2024年第2期21卷 690-717页

作者： Furquan AHMAD Pijush sAMUI s.s.MIsHRA Department of Civil Engineering National Institute of TechnologyPatna 800006India

The maintenance of safety and dependability in rail and road embankments is of utmost importance in order to facilitate the smooth operation of transportation *** study introduces a comprehensive methodology for soil slope stability evaluation,employing Monte Carlo simulation(MCs)and subset simulation(ss)with the"UPss 3.0 Add-in"in *** on an 11.693-meter embankment with a soil slope(inclination ratio of 2H:1V),the investigation considers earthquake coefficients(kh)and pore water pressure ratios(ru)following Indian zoning *** chance of slope failure showed a considerable increase as the Coefficient of Variation(COV),seismic coefficients(kh),and pore water pressure ratios(ru)experienced an *** ss approach showed exceptional efficacy in calculating odds of failure that are notably *** computational modeling,the study optimized the worst-case scenario using ANFIs-GA,ANFIs-GWO,ANFIs-PsO,and ANFIs-BBO *** ANFIs-PsO model exhibits exceptional accuracy(training R2=0.9011,RMsE=0.0549;testing R2=0.8968,RMsE=0.0615),emerging as the most *** study highlights the significance of conducting thorough risk assessments and offers practical insights into evaluating and improving the stability of soil slopes in transportation *** findings contribute to the enhancement of safety and reliability in real-world situations.

关键词： Monte Carlo simulation subset simulation Machine Learning seismic coefficient

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Detection and clearance in Alzheimer’s disease: leading with illusive chemical, structural and morphological features of the targets

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Neural Regeneration Research 2024年第3期19卷 497-498页

作者： Luís Gales i3s−Instituto de Investigação e Inovação em saúde Rua Alfredo AllenPortoPortugal(Gales L)IBMC−Instituto de Biologia Molecular e CelularUniversidade do PortoRua Alfredo AllenPortoPortugal ICBAs−Instituto de Ciências Biomédicas Abel salazar Rua de Jorge Viterbo FerreiraPortoPortugal

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex *** same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance ***,interference in biological systems is not that *** a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

关键词： Alzheimer diagnosis thereby

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