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SARS-CoV-2 ORF10 hijacking ubiquitination machinery reveals potential unique drug targeting sites

ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 4164-4173页

作者： Zhu, Kaixiang Song, Lili Wang, Linyue Hua, Lei Luo, Ziyu Wang, Tongyun Qin, Bo Yuan, Shuofeng Gao, Xiaopan mi, wenyi Cui, Sheng Chinese Acad Med Sci & Peking Union Med Coll Natl Inst Pathogen Biol NHC Key Lab Syst Biol Pathogens Beijing 100730 Peoples R China Peking Union Med Coll Key Lab Pathogen Infect Prevent & Control Minist Educ Beijing 100730 Peoples R China Yanan Univ Med Sch Yanan 716000 Shaanxi Peoples R China Tianjin Med Univ Tianjin Med Univ Gen Hosp Prov & Minist Cosponsored Collaborat Innovat Ctr M Dept ImmunolKey Lab Immune Microenvironm & DisMi Tianjin 300070 Peoples R China Univ Hong Kong Li Ka Shing Fac Med State Key Lab Emerging Infect Dis Pokfulam Hong Kong Peoples R China Univ Hong Kong Dept Microbiol Li Ka Shing Fac Med Pokfulam Hong Kong Peoples R China

Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2(ZYG11B) known as the substrate receptor of cullin-2 RING E3 ligase, is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity, leading to degradation of IFT46, a protein component of the intraflagellar transport (IFT) complex B. This results in dysfunctional cilia, which explains certain symptoms that are specific to COVID-19. However, the precise molecular mechanism of how ORF10 recognizes CUL2(ZYG11B) remains unknown. Here, we determined the crystal structure of CUL2(ZYG11B) complexed with the N-terminal extension (NTE) of SARS-CoV-2 ORF10 (2.9 & Aring;). The structure reveals that the ORF10 N-terminal heptapeptide (NTH) mimics the Gly/N-degron to bind CUL2(ZYG11B). Mutagenesis studies identified key residues within ORF10 that are key players in its interaction with CUL2(ZYG11B) both in ITC assay and in vivo cells. In addition, we prove that enhancement of CUL2(ZYG11B) activity for IFT46 degradation by which ORF10-mediated correlates with the binding affinity between ORF10 and CUL2(ZYG11B). Finally, we used a Global Protein Stability system to show that the NTH of ORF10 mimics the Gly/N-degron motif, thereby binding competitively to CUL2(ZYG11B) and inhibiting the degradation of target substrates bearing the Gly/N-degron motif. Overall, this study sheds light on how SARS-CoV-2 ORF10 exploits the ubiquitination machinery for proteasomal degradation, and offers valuable insights for optimizing PROTAC-based drug design based on NTH CUL2(ZYG11B) interaction, while pinpointing a promising target for the development of treatments for COVID-19. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article underthe CC BY license (http://***/licenses/by/4.0/).

关键词： SARS-CoV-2 ORF10 Crystal structure cullin-2 RING E3 ligase Drug design

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Analyzing topics in social media for improving digital twinning based product development

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Digital Communications and Networks 2024年第2期10卷 273-281页

作者： wenyi Tang Ling Tian Xu Zheng Ke Yan School of Computer Science and Engineering University of Electronic Science and Technology of ChinaChengdu611731China

Digital twinning enables manufacturers to create digital representations of physical entities,thus implementing virtual simulations for product *** efforts of digital twinning neglect the decisive consumer feedback in product development stages,failing to cover the gap between physical and digital *** work mines real-world consumer feedbacks through social media topics,which is significant to product *** specifically analyze the prevalent time of a product topic,giving an insight into both consumer attention and the widely-discussed time of a *** primary body of current studies regards the prevalent time prediction as an accompanying task or assumes the existence of a preset ***,these proposed solutions are either biased in focused objectives and underlying patterns or weak in the capability of generalization towards diverse *** this end,this work combines deep learning and survival analysis to predict the prevalent time of *** propose a specialized deep survival model which consists of two *** first module enriches input covariates by incorporating latent features of the time-varying text,and the second module fully captures the temporal pattern of a rumor by a recurrent network ***,a specific loss function different from regular survival models is proposed to achieve a more reasonable *** experiments on real-world datasets demonstrate that our model significantly outperforms the state-of-the-art methods.

关键词： Digital twinning Product development Topic analysis Social media

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Multi-wavelength nanowire micro-LEDs for future high speed optical communication

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Opto-Electronic Advances 2024年第3期7卷 1-3页

作者： Ayush Pandey Zetian mi Department of Electrical Engineering and Computer Science University of MichiganAnn ArborMI 48109USA

The future of optoelectronics is directed towards small-area light sources,foremost being ***,their use has been inhibited so far primarily due to fabrication and integration challenges,which impair efficiency and ***,bottom-up nanostructures grown using selective area epitaxy have garnered attention as a solution to the aforementioned *** Fu *** used this technique to demonstrate uniform p-i-n core-shell InGaAs/InP nanowire array light emitting *** devices are capable of voltage and geometry-controlled multi-wavelength and high-speed *** publication accentuates the wide capabilities of bottom-up nanostructures to resolve the difficulties of nanoscale optoelectronics.

关键词： communication high operations

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New insights on the high-corrosion resistance of UHP Mg-Ge alloys tested in a simulated physiological environment

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Journal of Magnesium and Alloys 2024年第3期12卷 1026-1044页

作者： Ting Liu Xingrui Chen Jeffrey Venezuela Yuan Wang Zhiming Shi wenyi Chen Matthew Dargusch Centre for Advanced Materials Processing and Manufacturing(AMPAM) School of Mechanical and Mining Engineeringthe University of QueenslandBrisbaneQLD 4072Australia CSIRO mineral Resources 1 Technology CourtPullenvaleQLD 4069Australia

UHP Mg-Ge alloys was recently found to provide excellent corrosion *** paper provides new insights on the mechanism of improved corrosion resistance of UHP Mg-Ge alloys in Hanks’*** studied UHP Mg-0.5Ge and UHP Mg-1Ge alloys showed superior corrosion resistance compared to UHP Mg and WE43,with the Mg-1Ge exhibiting the best corrosion *** exceptional corrosion resistance of the UHP alloy is attributed to(i)Mg_(2)Ge’s ability to suppress cathodic kinetics,(ii)Ge’s capability to accelerate the formation of a highly passive layer,and the(iii)low amounts of corrosion-accelerating impurities.

关键词： UHP Mg-Ge alloy Cathodic kinetics suppression Biodegradable metals In vitro corrosion Magnesium corrosion.

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SCIRD: Revealing Infection of Malicious Software in Edge Computing-Enabled IoT Networks

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Computers, Materials & Continua 2024年第5期79卷 2743-2769页

作者： Jiehao Ye Wen Cheng Xiaolong Liu wenyi Zhu Xuan’ang Wu Shigen Shen School of Information Engineering Huzhou UniversityHuzhou313000China

The Internet of Things(IoT)has characteristics such as node mobility,node heterogeneity,link heterogeneity,and topology *** the face of the IoT characteristics and the explosive growth of IoT nodes,which brings about large-scale data processing requirements,edge computing architecture has become an emerging network architecture to support IoT applications due to its ability to provide powerful computing capabilities and good service ***,the defense mechanism of Edge Computing-enabled IoT Nodes(ECIoTNs)is still weak due to their limited resources,so that they are susceptible to malicious software spread,which can compromise data confidentiality and network service *** this situation,we put forward an epidemiology-based susceptible-curb-infectious-removed-dead(SCIRD)***,we analyze the dynamics of ECIoTNs with different infection levels under different initial conditions to obtain the dynamic differential ***,we establish the presence of equilibrium states in the SCIRD ***,we conduct an analysis of the model’s stability and examine the conditions under which malicious software will either spread or disappear within Edge Computing-enabled IoT(ECIoT)***,we validate the efficacy and superiority of the SCIRD model through MATLAB *** research findings offer a theoretical foundation for suppressing the propagation of malicious software in ECIoT *** experimental results indicate that the theoretical SCIRD model has instructive significance,deeply revealing the principles of malicious software propagation in ECIoT *** study solves a challenging security problem of ECIoT networks by determining the malicious software propagation threshold,which lays the foundation for buildingmore secure and reliable ECIoT networks.

关键词： Edge computing Internet of Things malicious software propagation model heterogeneity

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Wide‑field swept‑source OCT angiography of the periarterial capillary‑free zone before and after anti‑VEGF therapy for branch retinal vein occlusion

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Eye and Vision 2024年第2期10卷 31-40页

作者： wenyi Tang Wei Liu Jingli Guo Lili Zhang Gezhi Xu Keyan Wang Qing Chang Department of Ophthalmology Eye and ENT Hospital of Fudan University83 Fenyang RoadShanghai 200031China Shanghai Key Laboratory of Visual Impairment and Restoration Fudan UniversityShanghaiChina NHC Key Laboratory of Myopia(Fudan University) Laboratory of MyopiaChinese Academy of Medical SciencesShanghaiChina

Background:The aim of the study was to investigate the changes in the periarterial capillary-free zone(paCFZ)after anti-vascular endothelial growth factor(VEGF)therapy in patients with branch retinal vein occlusion(BRVO)by widefield swept-source optical coherence tomography angiography(SS-OCTA)and assess their associations with clinical ***:In this retrospective observational study of 54 treatment-naive BRVO patients with macular edema,we reviewed the findings of 12×12 mm^(2)SS-OCTA at baseline,3,6,and 12 months after intravitreal ranibizumab *** paCFZ and major retinal artery areas were measured on SS-OCTA *** paCFZ area to artery area(P/A)ratio was ***:The paCFZ areas and P/A ratios of first-and second-order arteries were significantly greater in BRVO eyes than in contralateral eyes(all P<0.01),but there were no differences in the first-and second-order artery areas(P=0.20 and 0.25,respectively).The paCFZ areas and P/A ratios decreased significantly at 3,6,and 12 months after anti-VEGF therapy(all P<0.01).The baseline P/A ratio was significantly correlated with the baseline best-corrected visual acuity(BCVA),central retinal thickness,and their improvements at 3,6,and 12 months(all P<0.05).Baseline BCVA and P/A ratios of first-and second-order arteries were independently associated with the final BCVA in multivariate linear ***:Wide-field SS-OCTA shows that anti-VEGF therapy can lead to a significant improvement in the paCFZ parameters in *** baseline P/A ratios on SS-OCTA tend to predict better visual outcomes at 12 months after anti-VEGF therapy.

关键词： Swept-source optical coherence tomography angiography Branch retinal vein occlusion Periarterial capillary free zone Anti-VEGF treatment Prognosis

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Elevated CO_(2) increases soil redox potential by promoting root radial oxygen loss in paddy field

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Journal of Environmental Sciences 2024年第2期136卷 11-20页

作者： Jie Li Han Zhang wenyi Xie Cheng Liu Xiaoyu Liu Xuhui Zhang Lianqing Li Genxing Pan Institute of Resource Ecosystem and Environment of AgricultureNanjing Agricultural UniversityNanjing 210095China College of Agriculture Nanjing Agricultural UniversityNanjing 210095China

Soil redox potential(Eh)plays an important role in the biogeochemical cycling of soil *** its effect soil process and nutrients'availability under elevated atmospheric CO_(2) concentration and warming has seldom been ***,in this study,a field experiment was used to elucidate the effect of elevated CO_(2) concentration and warming on soil Eh,redox-sensitive elements and root radial oxygen loss(ROL).We hypothesized elevated CO_(2) and warming could alter soil Eh by promoting or inhibiting *** found that soil Eh in the rhizosphere was significantly higher than that of *** CO_(2) enhanced soil Eh by 11.5%,which corresponded to a significant decrease in soil Fe^(2+)and Mn^(2+)*** elevated CO_(2),the concentration of Fe^(2+)and Mn^(2+)decreased by 14.7%and 13.7%,*** also found that elevated CO_(2) altered rice root aerenchyma structure and promoted rice root *** elevated CO_(2),rice root ROL increased by 79.5%and 112.2%for Yangdao 6 and Changyou 5,*** had no effect on soil Eh and rice root *** warming increased the concentration of Mn^(2+)and SO_(4)^(2-)by 4.9%and 19.3%,*** was a significant interaction between elevated CO_(2) and warming on Fe^(2+)and Mn^(2+).Under elevated CO_(2),warming had no effect on the concentration of Fe^(2+)but decreased Mn^(2+)concentration *** study demonstrated that elevated atmospheric CO_(2) in the future could increase soil Eh by promoting rice root ROL,which will alter some soil nutrients'availability,such as Fe^(2+)and Mn^(2+).

关键词： Atmospheric CO_(2)enrichment Global warming Soil redox potential FACE Rice root aerenchyma

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Theoretical study on the stability of nanobubbles and its verification in molecular dynamics simulation

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Particuology 2024年第4期87卷 99-105页

作者： Sheng mi Chaofeng Hou Wei Ge School of Chemical Engineering and Technology Tianjin UniversityTianjin300072China State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing.100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China

The stability of vapor nanobubbles in bulk liquid was investigated theoretically and the critical bubble size was derived from macroscale thermodynamic equations,below which the system destabilizes with sharp drop in *** critical size was quantitatively verified in molecular dynamic simulation using the Lennard-Jones model of argon,where stronger attraction between the molecules at lower density is found to contribute most to the drop of system pressure and,as the Laplace pressure on the curved bubble interface fails to balance the pressure difference across the interface,the bubbles become *** theoretical model could be extended to other systems where reliable equations of state and interfacial tension are available.

关键词： Nanobubble Stability Phase diagram Critical size

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Ion Dynamics in Concentrated Electrolyte Solutions:Relating Equilibrium Fluctuations of the Ions to Transport Properties in Battery Cells

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Energy & Environmental Materials 2024年第1期7卷 131-138页

作者： Bernhard Roling Vanessa miß Janosch Kettner Department of Chemistry University of MarburgHans-Meerwein-Str.435032 MarburgGermany

In recent years,the interest in the development of highly concentrated electrolyte solutions for battery applications has increased *** electrolyte solutions are typically characterized by a low flammability,a high thermal and electrochemical stability and by the formation of a stable solid electrolyte interphase(SEI)in contact to electrode ***,the classification of concentrated electrolyte solutions in terms of the classical scheme"strong"or"weak"has been controversially discussed in the *** this paper,a comprehensive theoretical framework is presented for a more general classification,which is based on a comparison of charge transport and mass *** combining the Onsager transport formalism with linear response theory,center-of-mass fluctuations and collective translational dipole fluctuations of the ions in equilibrium are related to transport properties in a lithium-ion battery cell,namely mass transport,charge transport and Li^(+)transport under anion-blocking *** relevance of the classification approach is substantiated by showing that i)it is straightforward to classify highly concentrated electrolytes and that ii)both fast charge transport and fast mass transport are indispensable for achieving fast Li^(+)transport under anion-blocking conditions.

关键词： batteries concentrated electrolytes linear response theory Onsager formalism transport

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Analysis of particle dispersion and cavity formation during bulk particle water entry using fully coupled CFD-DEM-VOF approach

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Particuology 2024年第7期90卷 558-580页

作者： Utkan Çalışkan Sanja mišković Norman B.Keevil Institute of mining Engineering University of British Columbia2329 West MallVancouverBC V6T 1Z4Canada

This paper presents the development and validation of a fully coupled computational fluid dynamics—discrete element method—volume of fluid(CFD-DEM-VOF)model to simulate the complex behavior of particle-laden flows with free *** coupling between the fluid and particle phases is established through the implemented continuity,momentum,and alpha transport *** coupled particle forces such as drag,pressure gradient,dense virtual mass,viscous,and interface forces are also integrated,with drag and dense virtual mass forces being dependent on local *** integrated conservative alpha transport equation ensures phase volume conservation during interactions between particles and ***,we have implemented a trilinear interpolation method designed to operate on unstructured hexahedral *** method has been tested for its ability to properly resolve the coupling effects in the numerical simulations,particularly in cases with a relatively low cell-size *** model is validated through three distinct test cases:single particle water entry,dam break with particles,and water entry of a group of particles *** experimental setup is built to study the dynamics of the water entry of a group of particles,where three key flow features are analyzed:the evolution of average particle velocity,cavity shape,and particle dispersion cloud profiles in *** tests involve four different scenarios,including two different water levels(16.1 and 20.1 cm)and two different particle densities(2650 and 4000 kg/m3).High-speed videometry and particle tracking velocimetry(using ImageJ/TrackMate)methods are employed for experimental data *** is demonstrated that numerical results are in excellent agreement with theoretical predictions and experimental *** study highlights the significance of vortices in cavity shaping and particle *** validated CFD-DEM-VOF model constitutes a robust tool for simulating particle-laden flows,cont

关键词： CFD-DEM-VOF Trilinear interpolation Particle-laden flow Free-surface Particle water entry Volume conservation

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