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Hexokinase 1 and 2 mediates glucose utilization to regulate the synthesis of kappa casein via ribosome protein subunit 6 kinase 1 in bovine mammary epithelial cells

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Animal Nutrition 2024年第1期16卷 338-349页

作者： Tianyu Yang Jia Guo Han Song Osmond Datsomor Yuhang Chen Maocheng Jiang kang zhan.guoqi zhao Institute of Animal Culture Collection and Application College of Animal Science and Technology Yangzhou University

Glucose plays a vital part in milk protein synthesis through the mTOR signaling pathway in bovine mammary epithelial cells(BMEC). The objectives of this study were to determine how glucose affects hexokinase(HK) activity in BMEC and investigate the regulatory effect of HK in kappa casein(CSN3)synthesis via the mechanistic target of rapamycin complex 1(mTORC1) signaling pathway in BMEC. For this, HK1 and HK2 were knocked out in BMEC using the CRISPR/Cas9 system. The gene and protein expression, glucose uptake, and cell proliferation were measured. We found that glucose uptake, cell proliferation, CSN3 gene expression levels, and expression of HK1 and HK2 increased with increasing glucose concentrations. Notably, glucose uptake was significantly reduced in HK2 knockout(HK2KO)BMEC treated with 17.5 mM glucose. Moreover, under the same glucose treatment conditions, the proliferative ability and abundance of CSN3 were significantly diminished in both HK1 knockout(HK1KO)and HK2KO BMEC compared with that in wild-type BEMC. We further observed that the phosphorylation levels of ribosome protein subunit 6 kinase 1(S6K1) were reduced in HK1KO and HK2KO BMEC following treatment with 17.5 mM glucose. As expected, the levels of glucose-6-phosphate and the m RNA expression levels of glycolysis-related genes were decreased in both HK1KO and HK2KO BMEC following glucose treatment. These results indicated that the knockout of HK1 and HK2 inhibited cell proliferation and CSN3 expression in BMEC under glucose treatment, which may be associated with the inactivation of the S6K1 and inhibition of glycolysis.

关键词： Glucose Hexokinase Milk protein Mechanistic target of rapamycin complex 1 signaling pathway Bovine mammary epithelial cell Kappa casein

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Discovery of GluN2A subtype-selective N-methyl-d-aspartate(NMDA)receptor ligands

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1987-2005页

作者： Liyang Jiang Na Liu Fabao zhao Boshi Huang Dongwei kang Peng zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

The N-methyl-d-aspartate(NMDA)receptors,which belong to the ionotropic Glutamate receptors,constitute a family of ligand-gated ion *** the various subtypes of NMDA receptors,the GluN1/2A subtype plays a significant role in central nervous system(CNS)*** present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors,encompassing negative allosteric modulators(NAMs),positive allosteric modulators(PAMs)and competitive ***,the ligands’structure–activity relationships(SARs)and the binding models of representative ligands are also discussed,providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

关键词： NMDA receptors GluN2A subtype Subtype-selective ligands SARs Protein ligand interactions

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Pan-genome analysis reveals a highly plastic genome and extensive secreted protein polymorphism in Puccinia striformis ***

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Journal of Genetics and Genomics 2024年第5期51卷 574-577页

作者： Jierong Wang Yuxi Peng Yiwen Xu Zhiru Li Gangming zhan Zhensheng kang Jing zhao College of Plant Protection Northwest A&F UniversityYanglingShaanxi 712100China State Key Laboratory of Crop Stress Biology for Arid Areas Northwest A&F UniversityYanglingShaanxi 712100China College of Life Science Northwest A&F UniversityYanglingShaanxi 712100China

The obligate biotrophic basidiomycete fungus Puccinia striformis ***(Pst)is the causative agent of wheat stripe(yellow)rust,a disease that results in severe damage to global wheat production(Chen and kang,2017).This pathogen has a mixed reproductive mode encompassing both asexual and sexual *** asexual stage is accomplished by reinfecting wheat with urediniospores,while the sexual cycle involves five different spore types and two phylogenetically unrelated plant hosts wheat,which is the primary host,and barberry,which is the alternate host(zhao et al.,2016).This extremely complex lifecycle facilitates large genetic variation among Pst populations,which is conducive to the emergence of new virulent races that can overcome wheat resistance genes,resulting in epidemics(Chen and kang,2017).Secreted effector proteins,the key virulence factors in fungal pathogens,can not only suppress plant immune systems but also trigger host immune responses following recognition by plant receptors(Toruno et al.,2016).

关键词： Puccinia overcome wheat

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Kinetic model of vibration screening for granular materials based on biological neural network

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Particuology 2024年第5期88卷 98-106页

作者： zhan zhao Yan zhang Fang Qin Mingzhi Jin School of Agricultural Engineering Jiangsu UniversityZhenjiang212013China Shandong Academy of Agricultural Machinery Sciences Ji'nan250100China

The kinetic model is the theoretical basis for optimizing the structure and operation performance of vibration screening *** this paper,a biological neurodynamic equation and neural connections were established according to the motion and interaction properties of the material under vibration *** material feeding to the screen and the material passing through apertures were considered as excitatory and inhibitory inputs,respectively,and the generated stable neural activity landscape was used to describe the material distribution on the 2D screen *** dynamic process of material vibration screening was simulated using discrete element method(DEM).By comparing the similarity between the material distribution established using biological neural network(BNN)and that obtained using DEM simulation,the optimum coefficients of BNN model under a certain screening parameter were determined,that is,one relationship between the BNN model coefficients and the screening operation parameters was *** screening parameters were randomly selected,and the corresponding relationships were established as a ***,with straw/grain ratio,aperture diameter,inclination angle,vibration strength in normal and tangential directions as inputs,five independent adaptive neuro-fuzzy inference systems(ANFIS)were established to predict the optimum BNN model coefficients,*** training results indicated that ANFIS models had good stability and *** flexibility and adaptability of the proposed BNN method was demonstrated by modeling material distribution under complex feeding conditions such as multiple regions and non-uniform rate.

关键词： Kinetic model Material distribution Vibration screening Biological neural network DEM simulation Adaptive neuro-fuzzy inference systems

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Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： zhao Wang Heng zhang Zhen Gao Zihao Sang Erik De Clercq Christophe Pannecouque Dongwei kang Peng zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase *** fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design *** of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and ***,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization ***,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for *** importantly,23h was characterized by good pharmacokinetic properties and excellent safety in ***,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

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Chirality transfer induced circularly polarized luminescence of achiral dye molecules by plasmonic nanohelicoid

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Nano Research 2024年第9期17卷 8408-8414页

作者： Han Gao ChunLian zhan Tianqi zhao Jianzhong Zheng College of Optical and Electronic Technology China Jiliang UniversityHangzhou 310018China School of Environmental Science and Engineering Nanjing Tech UniversityNanjing 211816China

Optical materials with circularly polarized luminescence(CPL)features have attracted a growing interest due to their crucial role in biological sensing,display,spintronics,information storage,and so ***,CPL emissions in hybrid nanoparticle systems,in particular,chirality transfer induced CPL from chiral plasmonic nanoparticles,have rarely been explored due to a lack of effective bottom-up synthesis ***,we creatively take advantage of the newly introduced chiral plasmonic nanoparticles-gold nanohelicoid(GNH)to excite the CPL of achiral Rhodamine 6G(R6G).The fabricated GNH@R6G-SiO_(2)shows obvious CPL signals with|g_(lum)|up to *** with the single GNH,the photoluminescence(PL)dissymmetry factor of the single GNH@R6G-SiO_(2)is similar,but with 25 folds higher PL intensities under different circular *** research not only offers an effective and feasible method to fabricate single-particle level CPL-active materials,but also provides guidelines on how to regulate the CPL of achiral luminophores from chiral plasmonic nanostructures,thereby enlarging the category and quantity of CPL-active materials that can be applied for photonic technologies and visualization biosensing,especially some intracellular chirality related detection.

关键词： circularly polarized luminescence gold nanohelicoids chiral plasmonic

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Deadline-Constrained and Cost-Effective Multi-Workflow Scheduling with Uncertainty in Cloud Control Systems

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Journal of Systems Science & Complexity 2024年第5期37卷 1861-1886页

作者： YE Lingjuan YANG Liwen XIA Yuanqing zhan Yufeng zhao Xinchao School of Science Beijing University of Posts and TelecommunicationsBeijing 100876China Key Laboratory of Mathematics and Information Networks Beijing University of Posts and TelecommunicationsMinistry of EducationBeijing 100876China School of Automation Nanjing University of Information Science and TechnologyNanjing 210044China School of Automation Beijing Institute of TechnologyBeijing 100081China

In cloud control systems,generating an efficient and economical workflow scheduling strategy for deadline-constrained workflow applications,especially in uncertain multi-workflow dynamic scheduling processes,is a crucial *** optimize the total cost of workflow scheduling,the authors propose a cost-driven heuristic scheduling algorithm F-MWSA which consists of two phases:Fuzzy deadline distribution and fuzzy task *** the fuzzy deadline distribution phase,a new workflow deadline distribution strategy with fuzziness is designed to obtain the sub-deadline constraint of each *** fuzzy task scheduling phase focuses on a cost-effective strategy to assign tasks to cloud resources,reducing multi-workflow scheduling *** evaluations on five real-world workflows demonstrate that the proposed F-MWSA outperforms the baseline policy in terms of total cost,success ratio,resource utilization,and makespan.

关键词： Cloud computing cost-effective deadline constraint multi-workflow scheduling uncertainty

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Reduced-complexity multiple parameters estimation via toeplitz matrix triple iteration reconstruction with bistatic MIMO radar

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Chinese Journal of Aeronautics 2024年第7期37卷 482-495页

作者： Chenghong zhan Guoping HU Junpeng SHI Fangzheng zhao Hao ZHOU Graduate College Air Force Engineering UniversityXi’an 710051China Air and Missile Defense College Air Force Engineering UniversityXi’an 710051China College of Electronic Countermeasure National University of Defense TechnologyHefei 230037China Beijing Aeronautical Technology Research Center Beijing 100076China

In this advanced exploration, we focus on multiple parameters estimation in bistatic Multiple-Input Multiple-Output(MIMO) radar systems, a crucial technique for target localization and imaging. Our research innovatively addresses the joint estimation of the Direction of Departure(DOD), Direction of Arrival(DOA), and Doppler frequency for incoherent targets. We propose a novel approach that significantly reduces computational complexity by utilizing the TemporalSpatial Nested Sampling Model(TSNSM). Our methodology begins with a multi-linear mapping mechanism to efficiently eliminate unnecessary virtual Degrees of Freedom(DOFs) and reorganize the remaining ones. We then employ the Toeplitz matrix triple iteration reconstruction method, surpassing the traditional Temporal-Spatial Smoothing Window(TSSW) approach, to mitigate the single snapshot effect and reduce computational demands. We further refine the highdimensional ESPRIT algorithm for joint estimation of DOD, DOA, and Doppler frequency, eliminating the need for additional parameter pairing. Moreover, we meticulously derive the Cramér-Rao Bound(CRB) for the TSNSM. This signal model allows for a second expansion of DOFs in time and space domains, achieving high precision in target angle and Doppler frequency estimation with low computational complexity. Our adaptable algorithm is validated through simulations and is suitable for sparse array MIMO radars with various structures, ensuring higher precision in parameter estimation with less complexity burden.

关键词： MIMO Radar Multipleparameters estimation Temporal-spatial Nested Sampling Multi-linear mapping mechanism Toeplitz matrix triple iteration reconstruction Reduce computational complexity

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Coherence entropy during propagation through complex media

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Advanced Photonics 2024年第4期6卷 25-35页

作者： Xingyuan Lu Zhuoyi Wang Qiwen zhan Yangjian Cai Chengliang zhao Soochow University School of Physical Science and TechnologyJiangsu Key Laboratory of Frontier Material Physics and DevicesSuzhouChina University of Shanghai for Science and Technology School of Optical-Electrical and Computer EngineeringShanghaiChina Shandong Normal University School of Physics and ElectronicsShandong Provincial Engineering and Technical Center of Light ManipulationsShandong Provincial Key Laboratory of Optics and Photonic DeviceJinanChina East China Normal University Joint Research Center of Light Manipulation Science and Photonic Integrated Chip of East China Normal University and Shandong Normal UniversityShanghaiChina

The deformation,flicker,and drift of a light field owing to complex media such as a turbulent atmosphere have limited its practical ***,research on invariants in randomly fluctuated light fields has garnered considerable attention in recent *** is a statistical property of light,while its full and quantitative characterization is ***,we successfully realize the orthogonal modal decomposition of partially coherent beams and introduce the application of coherence entropy as a global coherence characteristic of such randomly fluctuated light *** is demonstrated that coherence entropy remains consistent during propagation in a unitary system by unraveling complex *** representative examples,we study the robustness of coherence entropy for partially coherent beams as they propagate through deformed optical systems and turbulent *** entropy is anticipated to serve as a key metric for evaluating the propagation of partially coherent beams in complex *** study paves the way for a broader application scope of a customized low-coherence light field through nonideal optical systems and complex media.

关键词： complex media propagation invariant modal decomposition orbital angular momentum statistical optics coherence

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Microstructure evolution and mechanical properties of brazing joint for ultra-thin-walled Inconel 718 considering grain size effect and brazing temperature

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Chinese Journal of Aeronautics 2024年第2期37卷 541-556页

作者： Rui zhao Yueshuai SONG Hui kang Min WAN School of Mechanical Engineering and Automation Beihang UniversityBeijing 100191China Jiangxi Research Institute of Beihang University Jiangxi 330000China

The systematic investigation of the mechanical properties and microstructure evolution process of ultra-thin-walled Inconel 718 capillary brazing joints is of great significance because of the exceptionally high demands on its *** achieve this objective,this study investigates the impact of three distinct brazing temperatures and five typical grain sizes on the brazed joints’mechanical properties and microstructure evolution *** evolution analysis was conducted based on Electron Back Scatter Diffraction(EBSD),Scanning Electron Microscopy(SEM),X-Ray Diffraction(XRD),High-Resolution Transmission Electron Microscopy(HRTEM),and Focused Ion Beam(FIB).Besides,the mechanical properties and fracture behavior were studied based on the uniaxial tension tests and in-situ tension *** findings reveal that the brazing joint’s strength is higher for the fine-grain capillary than the coarse-grain one,primarily due to the formation of a dense branch structure composed of G-phase in the brazing *** effects of grain size,such as pinning and splitting,are amplified at higher brazing ***,micro-cracks initiate around brittle intermetallic compounds and propagate through the eutectic zone,leading to a cleavage fracture *** fracture stress of fine-grain specimens is higher than that of coarse-grain due to the complex micro-crack ***,this study contributes significantly to the literature by highlighting the crucial impact of grain size on the brazing properties of ultra-thin-walled Inconel 718 structures.

关键词： EYWORDS Ultra-thin-walled structure Brazing Inconel 718 Grain size effect Brazing temperature

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