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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： jian-bang xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou Jie Sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Design and Cryogenic Performance of a Hexapod Platform for a Large Ground-based Wide Field Survey Telescope

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Research in Astronomy and Astrophysics 2024年第1期24卷 178-187页

作者： Yang Yu xue-Wen Wang Yu Zhang Jia-Lin Sun Zhen-bang xu jian-Li Wang Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchun 130033China Chinese Academy of Sciences Key Laboratory of On-orbit Manufacturing and Integration for Space Optics System Changchun 130033China University of Chinese Academy of Sciences Beijing 100049China

The thermal gradient is an important factor that causes degradation to the image quality of telescopes. In order to ensure the accurate alignment of the primary focus unit and the primary mirror, the hexapod platform(as a corrector) is investigated in this paper. First, a ground-based telescope with 2.5 m aperture and 3.5 deg field of view is described. The telescope is under construction, and it is expected to be finished in 2023. Second, the hexapod platform with flexure hinges utilized to adjust the primary focus unit is proposed, which is applied as a ***, the inverse kinematics of the platform is established and an open-loop control system is built based on ***, the cryogenic performance test for the hexapod platform is performed. The experimental results show that the resolution and repeatability of the translation for the hexapod platform can be achieved at the micrometer *** resolution and repeatability of the rotation can be achieved at the arc-second level. Therefore, the cryogenic performance of the hexapod platform can meet the optical imaging requirements of the wide-field ground-based telescope. The kinematic analysis and cryogenic performance tests in the paper provide a technical reference for the precise alignment of the primary focus unit and the primary mirror, which can improve the imaging quality of the telescope.

关键词： methods:miscellaneous space vehicles:instruments telescopes miscellaneous

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Evidence-based practices in sustainable travel behavior intervention: A knowledge graph-based systematic review

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第2期11卷 293-311页

作者： jian Li Chenjie xu Key Laboratory of Road and Traffic Engineering of the Ministry of Education College of Transportation EngineeringTongji UniversityShanghai 201804China

Sustainable travel behavior intervention is an essential strategy to promote the development of urban *** interventions offer personalized strategies based on certain scenario and participants to promote its effectiveness over hard travel ***,personalized strategies may also bring about difficulties to identify the actual effect of the ***,based on current practice,to make full use of travel behavior interventions,it is necessary to construct a unified methodological evidencebased framework to assess the reliability and effectiveness of travel behavior intervention *** response to these issues,we applied evidence-based knowledge graph to the field of sustainable travel behavior interventions to help decision supporters design sustainable travel behavior interventions wisely and in turn avoid excessive use of hard travel *** introduced concept of evidence-based practice to conduct a systematic analysis concerning reliability and validity of current full volume empirical studies by dimensions of scenarios,types of interventions and *** addition,we took advantage of high extensivity and integrability of knowledge graph to organize evidence-based related *** of the systematic analysis shows that in terms of reliability of evidence,school intervention is the best scenario,knowledge incentive is the best intervention type and promoting public transit and walking proportion are the best ***,the reliability of interventions in workplace,belonging to reward and threat along with aiming at changing travel patterns generally and lowering travel carbon emission need to be *** the study,various research prospects are raised to promote evidence quality in the field of travel behavior intervention *** a pioneer study,our research contributes to the field of urban transportation in introducing concepts of evidence-based practice and enabling optimization and

关键词： Evidence-based decision-making Evidence assessment Knowledge graph Travel behavior intervention Sustainable travel

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Persymmetric adaptive polarimetric detection of subspace range-spread targets in compound Gaussian sea clutter

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Journal of Systems Engineering and Electronics 2024年第1期35卷 31-42页

作者： xu Shuwen HAO Yifan WANG Zhuo xuE jian National Key Laboratory of Radar Signal Processing Xidian UniversityXi’an 710071China Xi’an Electronic Engineering Research Institute Xi’an 710100China Beijing Institute of Radio Measurement Beijing 100039China School of Communications and Information Engineering Xi’an University of Posts and TelecommunicationsXi’an 710121China

This paper focuses on the adaptive detection of range and Doppler dual-spread targets in non-homogeneous and nonGaussian sea *** sea clutter from two polarimetric channels is modeled as a compound-Gaussian model with different parameters,and the target is modeled as a subspace rangespread target *** persymmetric structure is used to model the clutter covariance matrix,in order to reduce the reliance on secondary data of the designed *** adaptive polarimetric persymmetric detectors are designed based on the generalized likelihood ratio test(GLRT),Rao test,and Wald *** the proposed detectors have constant falsealarm rate property with respect to the clutter texture,the speckle covariance *** results on simulated and measured data show that three adaptive detectors outperform the competitors in different clutter environments,and the proposed GLRT detector has the best detection performance under different parameters.

关键词： sea clutter adaptive polarimetric detection compound Gaussian model subspace range-spread target persymmetric structure

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Adversarial data splitting for domain generalization

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Science China(Information Sciences) 2024年第5期67卷 28-42页

作者： Xiang GU jian SUN Zongben xu School of Mathematics and Statistics Xi'an Jiaotong University

Domain generalization aims to learn a model that is generalizable to an unseen target domain,which is a fundamental and challenging task in machine learning for out-of-distribution generalization. This paper proposes a novel domain generalization approach that enforces the learned model to be able to generalize well over the train/val subset splitting of the training dataset. This idea is modeled herein as an adversarial data splitting framework, formulated as a min-max optimization problem inspired by the metalearning approach. The min-max optimization problem is solved by iteratively splitting the training dataset into the training and val subsets to maximize the domain shift measured by the objective function and updating the model parameters to enable the model to generalize well from the training subset to the val subset by minimizing the objective function. This adversarial training approach does not assume the known domain labels of the training data; instead, it automatically investigates the “hard” splitting of the train/val subsets to learn the generalizable model. Extensive experimental results using three benchmark datasets demonstrate the superiority of this approach. In addition, we derive a generalization error bound for the theoretical understanding of our proposed approach.

关键词： domain generalization adversarial learning data splitting meta-learning out of distribution

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A Novel 3D Gait Model for Subject Identification Robust against Carrying and Dressing Variations

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Computers, Materials & Continua 2024年第7期80卷 235-261页

作者： jian Luo Bo xu Tardi Tjahjadi jian Yi College of Information Science and Engineering Hunan Normal UniversityChangsha410000China School of Engineering University ofWarwickCoventryCV47ALUK

Subject identification via the subject’s gait is challenging due to variations in the subject’s carrying and dressing conditions in real-life *** paper proposes a novel targeted 3-dimensional(3D)gait model(3DGait)represented by a set of interpretable 3DGait descriptors based on a 3D parametric body *** 3DGait descriptors are utilised as invariant gait features in the 3DGait recognition method to address object carrying and *** 3DGait recognitionmethod involves 2-dimensional(2D)to 3DGaitdata learningbasedon3Dvirtual samples,a semantic gait parameter estimation Long Short Time Memory(LSTM)network(3D-SGPE-LSTM),a feature fusion deep model based on a multi-set canonical correlation analysis,and SoftMax recognition ***,a sensory experiment based on 3D body shape and pose deformation with 3D virtual dressing is used to fit 3DGait onto the given 2D gait images.3Dinterpretable semantic parameters control the 3D morphing and dressing *** degree measurement determines the semantic descriptors of 2D gait images of subjects with various shapes,poses and ***,using the 2D gait images as input and the subjects’corresponding 3D semantic descriptors as output,an end-to-end 3D-SGPE-LSTM is constructed and ***,body shape,pose and external gait factors(3D-eFactors)are estimated using the 3D-SGPE-LSTM model to create a set of interpretable gait descriptors to represent the 3DGait Model,i.e.,3D intrinsic semantic shape descriptor(3DShape);3D skeleton-based gait pose descriptor(3D-Pose)and 3D dressing with other ***,the 3D-Shape and 3D-Pose descriptors are coupled to a unified pattern space by learning prior knowledge from the *** research on CASIA B,CMU MoBo,TUM GAID and GPJATK databases shows that 3DGait is robust against object carrying and dressing variations,especially under multi-cross variations.

关键词： Gait recognition human identification three-dimensional gait canonical correlation analysis

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SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl^(−) accumulation in respiratory epithelium

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Signal Transduction and Targeted Therapy 2022年第8期7卷 3080-3092页

作者： Lei Chen Wei-Jie Guan Zhuo-Er Qiu jian-bang xu xu Bai Xiao-Chun Hou Jing Sun Su Qu Ze-Xin Huang Tian-Lun Lei Zi-Yang Huang Jincun Zhao Yun-Xin Zhu Ke-Nan Ye Zhao-Rong Lun Wen-Liang Zhou Nan-Shan Zhong Yi-Lin Zhang School of Life Sciences Sun Yat-sen UniversityGuangzhouChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina Guangzhou Laboratory GuangzhouChina

SARS-CoV-2,the culprit pathogen of COVID-19,elicits prominent immune responses and cytokine *** Cl^(−)is a crucial regulator of host defense,whereas the role of Cl^(−)signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains *** using human respiratory epithelial cell lines,primary cultured human airway epithelial cells,and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge,we demonstrated that SARS-CoV-2 nucleocapsid(N)protein could interact with Smad3,which downregulated cystic fibrosis transmembrane conductance regulator(CFTR)expression via *** intracellular Cl^(−)concentration([Cl^(−)]i)was raised,resulting in phosphorylation of serum glucocorticoid regulated kinase 1(SGK1)and robust inflammatory *** or knockout of SGK1 abrogated the N protein-elicited airway ***,N protein promoted a sustained elevation of[Cl^(−)]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4(PDE4).Rolipram,a selective PDE4 inhibitor,countered airway inflammation by reducing[Cl^(−)]*** findings suggested that Cl^(−)acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 *** the Cl^(−)signaling pathway might be a novel therapeutic strategy for COVID-19.

关键词： inflammation respiratory epithelium

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Impact of initial fluctuations and nuclear deformations in isobar collisions

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Nuclear Science and Techniques 2024年第6期35卷 155-162页

作者： jian-Fei Wang Hao-Jie xu Fu-Qiang Wang Department of Modern Physics University of Science and Technology of ChinaHefei 230026China School of Science Huzhou UniversityHuzhou 313000China Strong-Coupling Physics International Research Laboratory(SPiRL) Huzhou UniversityHuzhou 313000China Department of Physics and Astronomy Purdue UniversityWest LafayetteIN 47907USA

Relativistic isobar^(96)_(44)Ru+^(96)_(44)Ru and^(96)_(40)Zr+^(96)_(40)Zrcollisions have revealed intricate differences in their nuclear size and shape,inspiring unconventional studies of nuclear structure using relativistic heavy ion *** this study,we investigate the relative differences in the mean multiplicityR_()and the secondR_(ε2)and third-order eccentricityR_(ε3)between isobar collisions using initial state Glauber *** is found that initial fluctuations and nuclear deformations have negligible effects on R_()in most central collisions,while both are important for the R_(ε2)and R_(ε3),the degree of which is sensitive to the underlying nucleonic or sub-nucleonic degree of *** features,compared to real data,may probe the particle production mechanism and the physics underlying nuclear structure.

关键词： Relativistic isobar collisions Initial fluctuations Nuclear deformation

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Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period

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Signal Transduction and Targeted Therapy 2024年第1期9卷 19-35页

作者： Danyi Ao xuemei He jian Liu Li xu State Key Laboratory of Biotherapy West China HospitalSichuan University610041 SichuanPeople’s Republic of China

The spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in significant casualties and put immense strain on public health systems worldwide,leading to economic recession and social *** response,various prevention and control strategies have been implemented globally,including vaccine and drug development and the promotion of preventive *** these strategies has effectively curbed the transmission of the virus,reduced infection rates,and gradually restored normal social and economic ***,the mutations of SARS-CoV-2 have led to inevitable infections and reinfections,and the number of deaths continues to ***,there is still a need to improve existing prevention and control strategies,mainly focusing on developing novel vaccines and drugs,expediting medical authorization processes,and keeping epidemic *** measures are crucial to combat the Coronavirus disease(COVID-19)pandemic and achieve sustained,long-term prevention,management,and disease ***,we summarized the characteristics of existing COVID-19 vaccines and drugs and suggested potential future directions for their ***,we discussed the COVID-19-related policies implemented over the past years and presented some strategies for the future.

关键词： prevention sustained approval

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Spherical Confinement Generates Entropic Force to Accelerate Polymer Chain Detachment

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Chinese Journal of Polymer Science 2024年第3期42卷 407-416,I0010页

作者： Yu-Shan Zheng jian-Ping Zhou Yan xu Kai Li Mechanical Engineering Xinjiang UniversityUrumqi 830002China

To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape of a Brownian particle from the potential well of the spring. However, as the free dangling length of the polymer chain increases, the conformational entropy of the chain is affected by geometric confinement. It means that the wall exerts a repulsive force on the chain, resulting in accelerated link detachment from a macroscopic perspective. In this work, we investigate the effect of entropy on the detachment rate in the case where the substrate is spherical. We demonstrate that spherical confinement accelerates chain detachment both inside and outside the sphere. An analytical expression for the mean detachment time of breakable links is given, which includes an additional pre-factor that is related to the partition function. Additionally, we analyze the expressions for entropic forces inside the sphere, outside the sphere, and on a flat wall, comparing their magnitudes to explain the difference in mean detachment time.

关键词： Polymer detachment Breakable link Entropic force Mean first passage time

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