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A SARS-CoV-2-specific CAR-T-cell model identifies felodipine,fasudil,imatinib,and caspofungin as potential treatments for lethal COVID-19

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Cellular & Molecular Immunology 2023年第4期20卷 351-364页

作者： in Xia Lun-zhi Yuan Ya-hong Hu Jun-yi Liu Guo-sheng Hu ruo-yao qi Tian-ying Zhang Hua-long Xiong Zao-zao Zheng Hong-wei Lin Jia-mo Zhang Chao Yu Ming Zhou Jian Ma Tong Cheng Ri-rong Chen Yi Guan Ning-shao Xia Wen Liu State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019(COVID-19)severity and ***,drugs that are effective against inflammation to treat lethal COVID-19 are still urgently ***,we constructed a SARS-CoV-2 spike protein-specific CAR,and human T cells infected with this CAR(SARS-CoV-2-S CAR-T)and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients,causing cytokine storm and displaying a distinct memory,exhausted,and regulatory T-cell ***1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in *** on this"two-cell"(CAR-T and THP1 cells)model,we screened an FDA-approved drug library and found that felodipine,fasudil,imatinib,and caspofungin were effective in suppressing the release of cytokines,which was likely due to their ability to suppress the NF-kB pathway in ***,fasudi,imatinib,and caspofungin were further demonstrated,although to different extents,to attenuate lethal inflammation,ameliorate severe pneumonia,and prevent mortality in a SARS-CoV-2-infected Syrian hamster model,which were also linked to their suppressive role in *** summary,we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput *** drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe,inexpensive,and easily accessible for immediateuseinmostcountries.

关键词： COVID-19 SARS-CoV-2 CAR-T anti-inflammation NF-kB pathway

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Development of a general circumferentially nonuniform heat transfer fuel rod model for subchannel analysis and application to helical fuel rods

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Science China Technological Sciences 2025年

作者： Junsen FU Junlong LI Xiaowen WANG qi ZHANG yao XIAO Hanyang GU School of Mechanical Engineering Shanghai Jiao Tong University Key Laboratory of Nuclear Power Systems and Equipment of the Ministry of Education Shanghai Jiao Tong University National Key Laboratory of Nuclear Reactor Technology Nuclear Power Institute of China State Key Laboratory of Nuclear Power Safety Technology and Equipment Shanghai Jiao Tong University

The subchannel analysis method is one of the most crucial transient safety analysis methods in the thermal design of nuclear reactors. The nonuniformity of circumferential heat transfer is slight in conventional pressurized water reactor (PWR)cores, but it is significant in advanced reactors with wire-wrapped or helical fuel rods. Predicting circumferentially nonuniform heat transfer behavior can be challenging owing to the complex geometry of helical fuel rods. In this study, a general circumferentially nonuniform heat transfer fuel rod (GCNF) model is developed to predict the fuel central temperature and circumferential heat flux and wall temperature. This model incorporates a refined two-dimensional fuel conduction model and circumferential nonuniform shape factor, addressing the dual factors contributing to the circumferential nonuniformity of helical fuel rods. An empirical correlation for the nonuniform shape factor is developed based on the computational fluid dynamics (CFD) results, and it is implemented to the subchannel code. The newly developed model is applied to a helical fuel annulus and validated by comparing the prediction results with CFD data. The maximum wall temperature predicted by the code is 1.15°C lower than the value calculated through CFD. In terms of the heat flux, the maximum value at the inner corner is22 kW lower than that obtained from the CFD prediction. The accurate prediction of circumferentially nonuniform heat transfer in helical fuel, concerning the surface heat flux and cladding temperature, addresses existing shortcomings in helical fuel subchannel analysis methods. Additionally, the capability to predict the fuel central temperature is essential for the safety analysis to determine whether fuel rods are melting. The generality of the model framework allows it to be used for the prediction of circumferential nonuniform heat transfer behavior in other types of fuel assemblies.

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Practical approach for detecting k-nonseparability of multipartite quantum states

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 32-48页

作者： Jie Guo Jinchuan Hou Xiaofei qi Kan He College of Mathematics Taiyuan University of Technology School of Mathematics and Statistics Shanxi University Key Laboratory of Complex Systems and Data Science of Ministry of Education Shanxi University

The instantaneous detection of entanglement in quantum states poses a significant challenge in the fields of quantum computation and quantum information, and there are no practical methods or tools to complete this task satisfactorily so far. We propose a sufficient and necessary criterion of k-nonseparability for any n-partite finite or infinite dimensional systems, 2 ≤ k ≤ n. This criterion serves as the foundation for a practical scheme designed to detect entanglement and k-nonseparability across multipartite finite-dimensional systems. To exemplify the application of our scheme, we have developed a software tool that facilitates swift and precise identification of entanglement, k-nonseparability, and genuine entanglement within n-qubit systems, specifically tailored for systems with 2 ≤ n ≤ 4.

关键词： multipartite systems entanglement states entanglement witnesses ${\bm~k}$-nonseparability

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Ammonia pyrolysis oxidation excited by nanosecond pulsed discharge:Global/fluid models hybrid solution

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Journal of Energy Chemistry 2025年第1期100卷 385-396页

作者： Mingming Zhang Hanyu Wu qi Chen Jiaxin Yang Bonan Liu School of Mechanical Electronic and Control Engineering Beijing Jiaotong University China University of Petroleum

The kinetic characteristics of plasma-assisted oxidative pyrolysis of ammonia are studied by using the global/fluid models hybrid solution ***,the stable products of plasma-assisted oxidative pyrolysis of ammonia are *** results show that the consumption of NH3/O2and the production of N2/H2change linearly with the increase of voltage,which indicates the decoupling of nonequilibrium molecular excitation and oxidative pyrolysis of ammonia at low ***,the detailed reaction kinetics mechanism of ammonia oxidative pyrolysis stimulated by a nanosecond pulse voltage at low pressure and room temperature is *** on the reaction path analysis,the simplified mechanism is *** detailed and simplified mechanism simulation results are compared with experimental data to verify the accuracy of the simplified ***,based on the simplified mechanism,the fluid model of ammonia oxidative pyrolysis stimulated by the nanosecond pulse plasma is established to study the pre-sheath/sheath behavior and the resultant consumption and formation of key *** results show that the generation,development,and propagation of the pre-sheath have a great influence on the formation and consumption of *** consumption of NH3by the cathode pre-sheath is greater than that by the anode pre-sheath,but the opposite is true for OH and O（1S）.However,within the sheath,almost all reactions do not ***,by changing the parameters of nanosecond pulse power supply voltage,it is found that the electron number density,electron current density,and applied peak voltages are not the direct reasons for the structural changes of the sheath and ***,the discharge interval has little effect on the sheath structure and gas mixture *** research results of this paper not only help to understand the kinetic promotion of non-equilibrium excitation in the process of oxidative pyrolysis but also help to explore th

关键词： Nanosecond pulsed discharge Ammonia Oxidative pyrolysis Fluid model Global model

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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo qi Han Tang Jianian Hu Siying Kang Song qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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Accurate quantification of the algebraic,multiplicative algebraic,and simultaneous iterative reconstruction techniques in ionosphere rebuilding based on the TIEGCM assessment

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Earth and Planetary Physics 2025年第1期9卷 117-126页

作者： Ao qi HaiBing Ruan Institute of Space Weather Nanjing University of Information Science and TechnologyNanjing 210044China Key Laboratory of Geospace Environment University of Science&Technology of ChinaChinese Academy of SciencesHefei 230026China

The algebraic reconstruction technique(ART),multiplicative algebraic reconstruction technique(MART),and simultaneous iterative reconstruction technique(SIRT)are computational methodologies extensively utilized within the field of computerized ionospheric tomography(CIT)to facilitate three-dimensional reconstruction of the ionospheric ***,reconstruction accuracy elicits recurrent disputes over its practical application,and people usually attribute this issue to incomplete and uneven coverage of the *** Thermosphere Ionosphere Electrodynamics General Circulation Model(TIEGCM)offers a reasonable physics-based ionospheric background and is widely utilized in ionospheric *** use the TIEGCM simulations as the targeted ionosphere because the current measurements are far from able to realistically reproduce the ionosphere in *** designations of satellite measurements are conducted to investigate the limiting performance of CIT methods in ionospheric *** to common practice,electron density distributions from outputs of the International Reference Ionosphere(IRI)model are used as the iterative initial value in CIT *** outcomes suggest that despite data coverage,iterative initial conditions also play an essential role in ionospheric *** particular,in the longitudinal sectors where the iterative initial height of the F2-layer peak electron density(hmF2)differs substantially from the background densities,none of the three CIT methods can reproduce the exact background *** hmF2 is close but the ionospheric F2-layer peak density(NmF2)is different between the targeted background and initial conditions,the MART performs better than the ART and SIRT,as evidenced by the correlation coefficients of MART being above 0.97 and those of ART and SIRT being below *** summary,this investigation reveals the potential uncertainties in traditional CIT reconstruction,particularly when reali

关键词： computerized ionospheric tomography International Reference Ionosphere model Thermosphere Ionosphere Electrodynamics General Circulation model ionosphere

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Electrocatalytic cleavage of a lignin β-O-4 model compound and coupling with nitrogen-containing aromatics using Prussian blue analogue-derived nickel–cobalt spinel

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Journal of Energy Chemistry 2025年第1期100卷 628-636页

作者： Yi qi Xueying Chen Bowen Liu Xuliang Lin Xueqing qiu Yanlin qin Guangdong Provincial Key Laboratory of Plant Resources Biorefinery School of Chemical Engineering and Light Industry Guangdong University of Technology Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center Guangdong Basic Research Center of Excellence for Ecological Security and Green Development Guangdong University of Technology

Electrochemical conversion of lignin for the production of high-value heterocyclic aromatic compounds has great *** demonstrate the targeted synthesis and cation modulation of NiCo2O4spinel nanoboxes,synthesized via cation exchange and calcination *** catalysts exhibit excellent efficacy in the electrocatalytic conversion of lignin model compounds,specifically 2-phenoxy-1-phenylethanol,into nitrogen-containing aromatics,achieving high conversion rates and *** catalysts were synthesized via a cation exchange and calcination oxidation process,using Prussian blue nanocubes as *** porous architecture and polymetallic composition of the NiCo2O4spinel demonstrated superior performance in electrocatalytic oxidative coupling,achieving a 99.2 wt%conversion rate of the 2-phenoxy-1-phenylethanol with selectivities of 37.5 wt%for quinoline derivatives and 31.5 wt%for *** innovations include the development of a sustainable one-pot synthesis method for quinoline derivatives,the elucidation of a multistage reaction pathway involving CAO bond cleavage,hydroxyaldol condensation,and CAN bond formation,and a deeper mechanistic understanding derived from DFT *** work establishes a new strategy for lignin valorization,offering a sustainable route to produce high-value nitrogen-containing aromatics from renewable biomass under mild conditions,without the need for additional reagents.

关键词： Spinel Biomass valorization Electrocatalysis Lignin oxidation Coupling

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei Niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan qi School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin University of Traditional Chinese Medicine TianjinChina Characteristic Medical Center of People’s Armed Police Forces TianjinChina Fujian Maternity and Child Health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

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Asymptotic false discovery control of the Benjamini-Hochberg procedure for pairwise comparisons

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Science China Mathematics 2025年第1期 223-252页

作者： Weidong Liu Dennis Leung qi-Man Shao School of Mathematical Sciences Shanghai Jiao Tong University School of Mathematics and Statistics University of Melbourne Department of Statistics and Data Science SICMSouthern University of Science and Technology

In a one-way analysis-of-variance(ANOVA) model,the number of pairwise comparisons can become large even with a moderate number of *** by this,we consider a regime with a growing number of groups and prove that,when testing pairwise comparisons,the Benjamini-Hochberg(BH) procedure can asymptotically control false discoveries,despite the fact that the involved t-statistics do not exhibit the wellknown positive dependence structure required for exact false discovery rate(FDR) *** Tukey's perspective that the difference between the means of any two groups cannot be exactly zero,our main result provides control over the directional false discovery rate and directional false discovery proportion.A key technical contribution of our work is demonstrating that the dependence among the t-statistics is sufficiently weak to establish the convergence result typically required for asymptotic FDR *** analysis does not rely on conventional assumptions such as normality,variance homogeneity,or a balanced design,thereby offering a theoretical foundation for applications in more general settings.

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