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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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p-d Orbital Hybridization Engineered Single-Atom Catalyst for Electrocatalytic Ammonia Synthesis

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Energy & Environmental Materials 2024年第2期7卷 123-129页

作者： Jingkun Yu Xue Yong Siyu Lu Green Catalysis center and College of Chemistry Zhengzhou University Department of Chemistry University of Sheffield

The rational design of metal single-atom catalysts（SACs） for electrochemical nitrogen reduction reaction（NRR） is challenging. Two-dimensional metal–organic frameworks（2DMOFs） is a unique class of promising SACs. Up to now, the roles of individual metals, coordination atoms, and their synergy effect on the electroanalytic performance remain unclear. Therefore, in this work, a series of 2DMOFs with different metals and coordinating atoms are systematically investigated as electrocatalysts for ammonia synthesis using density functional theory calculations. For a specific metal, a proper metalintermediate atoms p-d orbital hybridization interaction strength is found to be a key indicator for their NRR catalytic activities. The hybridization interaction strength can be quantitatively described with the p-/d-band center energy difference（Δd-p）, which is found to be a sufficient descriptor for both the p-d hybridization strength and the NRR performance. The maximum free energy change（ΔGmax） and Δd-p have a volcanic relationship with OsC4（Se）4located at the apex of the volcanic curve, showing the best NRR performance. The asymmetrical coordination environment could regulate the band structure subtly in terms of band overlap and *** work may shed new light on the application of orbital engineering in electrocatalytic NRR activity and especially promotes the rational design for SACs.

关键词： first-principle calculations Nitrogen reduction p-d orbital hybridization single-atom catalysts

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A general mirror equivalence theorem for coset vertex operator algebras

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Science China Mathematics 2024年第10期67卷 2237-2282页

作者： Robert McRae Yau Mathematical Sciences center Tsinghua University

We prove a general mirror duality theorem for a subalgebra U of a simple conformal vertex algebra A and its commutant V=ComA（U）.Specifically,we assume that ■ as a U■V-module,where the U-modules Uiare simple and distinct and are objects of a semisimple braided ribbon category of Umodules,and the V-modules Viare semisimple and contained in a（not necessarily rigid） braided tensor category of *** also assume U=ComA（V）.Under these conditions,we construct a braid-reversed tensor equivalence τ:uA→vA,where uAis the semisimple category of U-modules with simple objects Ui,i∈I,and vAis the category of V-modules whose objects are finite direct sums of *** particular,the V-modules Viare simple and distinct,and vAis a rigid tensor *** an application,we find a rigid semisimple tensor subcategory of modules for the Virasoro algebra at central charge 13+6p+6p-1,p∈Z≥2, which is braided tensor equivalent to an abelian 3-cocycle twist of the category of finite-dimensional ***,the Virasoro vertex operator algebra at central charge 13+6p+6p-1is the PSL2（C）-fixed-point subalgebra of a simple conformal vertex algebra w（-p）,analogous to the realization of the Virasoro vertex operator algebra at central charge 13-6p-6p-1as the PSL2（C）-fixed-point subalgebra of the triplet algebra W（p）.

关键词： vertex operator algebras coset conformal field theory braid-reversed tensor equivalence Virasoro algebra

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Programmable silicon-photonic quantum simulator based on a linear combination of unitaries

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Photonics Research 2024年第8期12卷 1760-1767页

作者： YUE YU YULIN CHI CHONGHAO ZHAI JIESHAN HUANG QIHUANG GONG JIANWEI WANG State Key Laboratory for Mesoscopic Physics School of Physics Peking University Frontiers Science center for Nano-optoelectronics & Collaborative Innovation center of Quantum Matter Peking University Collaborative Innovation center of Extreme Optics Shanxi University Yangtze Delta Institute of Optoelectronics Peking University Hefei National Laboratory

Simulating the dynamic evolution of physical and molecular systems in a quantum computer is of fundamental interest in many applications. The implementation of dynamics simulation requires efficient quantum algorithms. The Lie-Trotter-Suzuki approximation algorithm, also known as the Trotterization, is basic in Hamiltonian dynamics simulation. A multi-product algorithm that is a linear combination of multiple Trotterizations has been proposed to improve the approximation accuracy. However, implementing such multiproduct Trotterization in quantum computers remains challenging due to the requirements of highly controllable and precise quantum entangling operations with high success probability. Here, we report a programmable integrated-photonic quantum simulator based on a linear combination of unitaries, which can be tailored for implementing the linearly combined multiple Trotterizations, and on the simulator we benchmark quantum simulation of Hamiltonian dynamics. We modify the multi-product algorithm by integrating it with oblivious amplitude amplification to simultaneously reach high simulation precision and high success probability. The quantum simulator is devised and fabricated on a large-scale silicon-photonic quantum chip, which allows the initialization, manipulation, and measurement of arbitrary four-qubit states and linearly combined unitary gates. As an example, the quantum simulator is reprogrammed to emulate the dynamics of an electron spin and nuclear spin coupled system. This work promises the practical dynamics simulations of real-world physical and molecular systems in future large-scale quantum computers. ? 2024 Chinese Laser Press

关键词： Numerical simulation Quantum computation Quantum simulator Quantum technology Signal processing Silicon photonics

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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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A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance

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Journal of Genetics and Genomics 2024年第8期51卷 836-843页

作者： Shibo Hou Jingheng Chen Ruobing Feng Xuejiao Xu Nan Liang Jackson Champer center for Bioinformatics Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China

CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant *** operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a ***,resistance alleles formed by end-joining repair pose a significant *** address this,we create a homing drive targeting the essential hairy gene in Drosophila *** resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of *** drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the ***,the drive does not reach 100%due to the formation of functional resistance alleles despite using four *** alleles have a large deletion but likely utilize an alternate start ***,revised designs targeting more essential regions of a gene may be necessary to avoid such functional *** of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.

关键词： Genedrive Homing drive Rescueelement Population modification Multiplexed gRNAs Resistance alleles Cage study

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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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