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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

Neural Regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of Dayton Premedical Program University of Dayton center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton The Integrative Science and Engineering center University of Dayton center for Genomic Advocacy (TCGA) Indiana State University

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) virus, responsible for the coronavirus disease 2019(COVID-19) pandemic, induces symptoms including increased inflammatory response, severe acute respiratory syndrome(SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer’s disease remain understudied. Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye, we found that misexpression of nonstructural protein 3(Nsp3), a papain-like protease, ablates the eye and generates dark necrotic spots. Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters, terminal deoxynucleotidyl transferase(TdT) dUTP Nick-end labeling(TUNEL) assay, and dihydroethidium staining. Furthermore, Nsp3 misexpression activates both apoptosis and autophagy mechanism(s) to regulate tissue homeostasis. Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma, Neuro-2a cells, significantly reduced the metabolic activity of these cells and triggers cell death. Misexpression of SARS-CoV2 Nsp3 in an Alzheimer’s disease transgenic fly eye model(glass multiple repeats [GMR]>amyloid β42) further enhances the neurodegenerative rough eye phenotype due to increased cell death. These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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Global Stability to Steady Supersonic Rayleigh Flows in One-Dimensional Duct

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Chinese Annals of Mathematics,Series B 2024年第2期45卷 279-296页

作者： Fenglun WEI Jianli LIU Department of Mathematics Shanghai University Newtouch center for Mathematics of Shanghai university

Heat exchange plays an important role in hydrodynamical systems,which is an interesting topic in theory and *** this paper,the authors consider the global stability of steady supersonic Rayleigh flows for the one-dimensional compressible Euler equations with heat exchange,under the small perturbations of initial and boundary conditions in a finite rectilinear duct.

关键词： Compressible Euler equations Heat exchange Supersonic Rayleigh fow Steady solution Classical solution

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A FAS approach for stabilization of generalized chained forms: part 1. Discontinuous control laws

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Science China(Information Sciences) 2024年第2期67卷 118-143页

作者： Guang-Ren DUAN center for Control Theory and Guidance Technology Harbin Institute of Technology center for Control Science and Technology Southern University of Science and Technology

In this paper, a type of general nonholonomic systems is proposed, which contains both the Brockett’s two example systems, and their extended n-dimensional chained forms, as special cases. For the stabilization of such systems, a stabilizing controller is proposed based on the fully actuated system(FAS)approach, which is discontinuous at the origin but time-invariant when the open-loop system is time-invariant,and drives the feasible trajectories of the system to the origin exponentially. Furthermore, the proposed FAS approach is also extended to the sub-normal system case and the time-delay system case.

关键词： nonholonomic systems feedback stabilization exponential convergence sub-fully actuated systems time-delay systems

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Fantastic voyage: The journey of NLRP3 inflammasome activation

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Genes & Diseases 2024年第2期11卷 819-829页

作者： Xiangyong Que Sihao Zheng Qibin Song Huadong Pei Pingfeng Zhang Cancer center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA

NLRP3 inflammasome,an intracellular multiprotein complex,can be activated by a range of pathogenic microbes or endogenous hazardous *** activation results in the release of cytokines such as IL-1β and IL-18,as well as Gasdermin D which eventually causes *** activation of NLRP3 inflammasome is under strict control and regulation by numerous pathways and *** excessive activation can lead to a persistent inflammatory response,which is linked to the onset and progression of severe *** studies have revealed that the subcellular localization of NLRP3 changes significantly during the activation *** this review,we review the current understanding of the molecular mechanism of NLRP3 inflammasome activation,focusing on the subcellular localization of NLRP3 and the associated regulatory *** aim to provide a comprehensive understanding of the dynamic transportation,activation,and degradation processes of NLRP3.

关键词： Inflammasome activation Innate immunity NLRP3 NLRP3 inflammasome Subcellular localization

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Homeostatic regulation of NAD(H)and NADP(H)in cells

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Genes & Diseases 2024年第5期11卷 285-299页

作者： Luojun Chen Xiaoke Xing Pingfeng Zhang Lulu Chen Huadong Pei Cancer center Renmin Hospital of Wuhan UniversityWuhanHubei 430062China Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA

Nicotinamide adenine dinucleotide(NAD^(+))/reduced NAD^(+)(NADH)and nicotinamide adenine dinucleotide phosphate(NADP^(+))/reduced NADP^(+)(NADPH)are essential metabolites involved in multiple metabolic pathways and cellular ***^(+)and NADH redox couple plays a vital role in catabolic redox reactions,while NADPH is crucial for cellular anabolism and antioxidant *** NAD(H)and NADP(H)homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms,such as biosynthesis,consumption,recycling,and conversion between NAD(H)and NADP(H).The conversions between NAD(H)and NADP(H)are controlled by NAD kinases(NADKs)and NADP(H)phosphatases[specifically,metazoan SpoT homolog-1(MESH1)and nocturnin(NOCT)].NADKs facilitate the synthesis of NADP^(+)from NAD^(+),while MESH1 and NOCT convert NADP(H)into NAD(H).In this review,we summarize the physiological roles of NAD(H)and NADP(H)and discuss the regulatory mechanisms governing NAD(H)and NADP(H)homeostasis in three key aspects:the transcriptional and posttranslational regulation of NADKs,the role of MESH1 and NOCT in maintaining NAD(H)and NADP(H)homeostasis,and the influence of the circadian clock on NAD(H)and NADP(H)*** conclusion,NADKs,MESH1,and NOCT are integral to various cellular processes,regulating NAD(H)and NADP(H)*** of these enzymes results in various human diseases,such as cancers and metabolic ***,strategies aiming to restore NAD(H)and NADP(H)homeostasis hold promise as novel therapeutic approaches for these diseases.

关键词： MESH1 NAD(H) NADK NADP(H) Nocturnin

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Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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Pushing the boundaries: an interview with Dae-Hyun Kim on terahertz devices

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National Science Review 2024年第3期11卷 42-45页

作者： Defu Wang the center for Carbon-based Electronics School of Electronics Peking University

Ⅲ–Ⅴ compound semiconductors, such as InGaAs/InAlAs, exhibit exceptional carrier transport properties, establishing them as fundamental elements in terahertz(THz) applications crucial for the development of 6G netwo...

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Non-Gaussian feature of the output field from a double qubit-cavity ultrastrong coupling system

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Communications in Theoretical Physics 2024年第7期76卷 32-38页

作者： Sheng-wen Xu Shi-yu Dai Teng Zhao center for Quantum Science and Technology Jiangxi Normal University

We investigate the non-Gaussian feature of radiation in a circuit quantum electrodynamics(QED) system where two qubits are strongly coupled to a single-mode cavity. In the regime of ultrastrong coupling(USC), the rotating-wave approximation is not valid, and the Rabi Hamiltonian contains counter-rotating wave terms, leading to level crossing and avoided crossings in the energy spectrum. We further analyze the intensity-amplitude correlation of the output field in these two novel scenarios. In the USC regime, the creation and annihilation operators in the correlation function are replaced, allowing for the identification of non-Gaussian features in the output field. Our findings reveal that despite the absence of squeezing effects in the output light, significant non-Gaussian characteristics are present. Additionally, we demonstrate that as the driving or coupling strength increases, the non-Gaussian features of the output field become more pronounced. This suggests that USC systems hold broad potential applications in the realms of nonlinear optics and the generation of non-Gaussian states.

关键词： intensity-amplitude correlation non-Gaussian ultrastrong coupling

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Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope

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Thermally modulated photoelectronic synaptic behavior in HfS2/VO2 heterostructure

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Rare Metals 2024年第8期43卷 3798-3809页

作者： Le Wang Lin Wang Xiao-Yun Ye Xiong-Hu Xu Li-Yan Shang Ya-Wei Li Jin-Zhong Zhang Liang-Qing Zhu Zhi-Gao Hu Technical center for Multifunctional Magneto-Optical Spectroscopy (Shanghai) Engineering Research Center of Nanophotonics & Advanced Instrument (Ministry of Education) Department of PhysicsSchool of Physics and Electronic ScienceEast China Normal University Collaborative Innovation center of Extreme Optics Shanxi University

Neuromorphic computing is known for its efficient computational speed,low latency,and reduced power consumption,which is considered a pivotal technology to overcome the von Neumann *** synapses are an indispensable component of neuromorphic computational artificial neural *** guarantee effective and precise processing of optical signals,it must have a high responsivity,detectivity,and the ability to adapt to various ***,a synaptic transistor based on the HfS2/VO2heterojunction with a responsivity of8.6×10～3 A·W-1and a detectivity of 1.26×1014Jones at405 nm laser was ***,the typical synaptic behavior was successfully simulated,including postsynaptic currents（PSCs）,the transition from shortterm plasticity（STP） to long-term plasticity（LTP）.When VO2converts from the semiconductor state to the metal state,the HfS2/VO2heterojunction transforms into a Schottky heterojunction from a Type Ⅱ heterojunction with ***'s important,the heterojunction still exhibits excellent responsivity and detectivity,as well as stability of synaptic *** addition,the classical Pavlovian conditioning experiment is simulated under different laser intensity to study the brain's associative learning *** results demonstrate that the HfS2/VO2heterojunction synapse exhibits significant responsivity and detectivity and is adaptable to high-temperature environments,showing great potential for neuromorphic computational applic ations.

关键词： HfS 2 VO 2 Phase transition Photoelectric synapse Heterojunction

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