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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang liu Dongchao Shen Qing liu Mingsheng liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

Exponential Time Differencing Method for a Reaction-Diffusion System with Free Boundary

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Communications on Applied Mathematics and Computation 2024年第1期6卷 354-371页

作者： Shuang liu Xinfeng liu Department of Mathematics University of CaliforniaSan Diego9500 Gilman DriveLa JollaCalifornia92093-0112USA Department of Mathematics University of South CarolinaColumbiaSouth Carolina29208USA

For reaction-diffusion equations in irregular domains with moving boundaries,the numerical stability constraints from the reaction and diffusion terms often require very restricted time step sizes,while complex geometries may lead to difficulties in the accuracy when discretizing the high-order derivatives on grid points near the boundary.It is very challenging to design numerical methods that can efficiently and accurately handle both difficulties.Applying an implicit scheme may be able to remove the stability constraints on the time step,however,it usually requires solving a large global system of nonlinear equations for each time step,and the computational cost could be significant.Integration factor(IF)or exponential time differencing(ETD)methods are one of the popular methods for temporal partial differential equations(PDEs)among many other methods.In our paper,we couple ETD methods with an embedded boundary method to solve a system of reaction-diffusion equations with complex geometries.In particular,we rewrite all ETD schemes into a linear combination of specificФ-functions and apply one state-of-the-art algorithm to compute the matrix-vector multiplications,which offers significant computational advantages with adaptive Krylov subspaces.In addition,we extend this method by incorporating the level set method to solve the free boundary problem.The accuracy,stability,and efficiency of the developed method are demonstrated by numerical examples.

关键词： Reaction diffusion equations Free boundary Integrating factor method Level set method

CFD-DEM simulation of high density particles fluidization behaviors in 3D conical spouted beds

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Particuology 2024年第5期88卷 266-281页

作者： Lin Jiang Mofan Qiu Rongzheng liu Bing liu Youlin Shao Malin liu Institute of Nuclear and New Energy Technology Collaborative Innovation Center of Advanced Nuclear Energy TechnologyTsinghua UniversityBeijing 100084China

The spouted bed has been used in the coating process of high-density nuclear fuel particle.The particle fluidization behaviors in pseudo-2D and 3D spouted beds were simulated and validated.The effects of four independent variables(cone angle,particle density,inlet gas velocity,and particle loading)on particle fluidization behaviors in the 3D spouted bed were investigated systematically.The cone angle effect on fluidization mechanism was studied quantitatively first time.A new fluidization quality index was proposed based on the particle entrainment principle,and an extreme value was obtained when the cone angle was 60°,considered to be the optimum value for the 3D conical spouted bed.It was indicated the gas–solid contact efficiency can be kept up if the gas velocity was proportional toρp 0.65 and N p 0.78 when the particle density or loading was increased.These results will be useful for geometry and operation parameters design of the 3D conical spouted bed and helpful for developing the fluidization mechanism of high-density particles.

关键词： Spouted bed High-density particle CFD-DEM Fluidization quality index Particle loading

Risk factors for brain injury in patients with exertional heatstroke:A 5-year experience

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Chinese Journal of Traumatology 2024年第2期27卷 91-96页

作者： Li Zhong Ming Wu Zhe-Ying liu Yan liu Zhi-Feng liu Department of Traditional Chinese Medicine The First Affiliated HospitalGuizhou University of Chinese MedicineGuiyang550001China Department of Infection and Critical Care Medicine The Second People's Hospital of Shenzhen&First Affiliated Hospital of Shenzhen UniversityHealth Science CenterShenzhenGuangdong province518035China Department of Medical Critical Care Medicine General Hospital of Southem Theatre Command of PLA.Guangzhou510010China Guangdong Branch Center National Clinical Research Center for Geriatric Diseases(Chinese PLA General Hospital)Guangzhou510010China

Purpose:Minimal data exist on brain injury in patients with exertional heatstroke(EHS)in developing country.In this study,we explored the risk factors for brain injury induced by EHS 90-day after onset.Methods:A retrospective cohort study of patients with EHS was conducted in the intensive care unit of the General Hospital of Southern Theater Command of PLA in China from April 2014 to June 2019.Patients were divided into non-brain injury(fully recovered)and brain injury groups(comprising deceased patients or those with neurological sequelae).The brain injury group was further subdivided into a death group and a sequela group for detailed analysis.General information,neurological performance and information on important organ injuries in the acute stage were recorded and analysed.Multivariable logistic regression was used to identify risk factors for brain injury after EHS and mortality risk factors for brain injury,and Kaplan-Meier survival curve was used to evaluate the effect of the neurological dysfunction on survival.Results:Out of the 147 EHS patients,117 were enrolled,of which 96(82.1%)recovered,13(11.1%)died,and 8(6.8%)experienced neurological sequelae.Statistically significant differences were found between non-brain injury and brain injury groups in age,hypotension,duration of consciousness disorders,time to drop core body temperature below 38.5℃,lymphocyte counts,platelet counts,procalcitonin,alanine aminotransferase,aspartate aminotransferase,creatinine,cystatin C,coagulation parameters,international normalized ratio,acute physiology and chronic health evaluation II scores,sequential organ failure assessment(SOFA)scores,and Glasgow coma scale scores(all p<0.05).Multivariate logistic regression showed that age(OR=1.090,95%CI:1.02-1.17,p=0.008),time to drop core temperature(OR=8.223,95%CI:2.30-29.40,p=0.001),and SOFA scores(OR=1.676,95%CI:1.29-2.18,p<0.001)are independent risk factors for brain injury induced by EHS.The Kaplan-Meier curves suggest significantly prolonged survival(p<0.001)in patients with

关键词： Exertional heatstroke Brain injury Sequela Risk factors Disorders of consciousness

Control Strategies for Digital Twin Systems

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IEEE/CAA Journal of Automatica Sinica 2024年第1期11卷 170-180页

作者： Guo-Ping liu IEEE the Center for Control Science and Technology Southern University of Science and TechnologyShenzhen 518055China

With the continuous breakthrough in information technology and its integration into practical applications, industrial digital twins are expected to accelerate their development in the near future. This paper studies various control strategies for digital twin systems from the viewpoint of practical applications.To make full use of advantages of digital twins for control systems, an architecture of digital twin control systems, adaptive model tracking scheme, performance prediction scheme, performance retention scheme, and fault tolerant control scheme are proposed. Those schemes are detailed to deal with different issues on model tracking, performance prediction, performance retention, and fault tolerant control of digital twin systems. Also, the stability of digital twin control systems is analysed. The proposed schemes for digital twin control systems are illustrated by examples.

关键词： Digital twin control systems fault tolerant control model tracking performance prediction performance retention

HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

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Science Bulletin 2024年第2期69卷 173-178页

作者： Siyuan Jiang Xiaoqi Han Tihui liu Ying He Zidong Zhao Tongfeng liu Shuwen Cheng Jihang Zhang Liqiang Duan Yajuan liu Tianyou Cheng Yong liu Qinong Ye Shan Gao Zhongda Hospital Medical SchoolAdvanced Institute for Life and HealthSoutheast UniversityNanjing 20096China Medical School of Guizhou University Guiyang 550025China Shanxi Academy of Advanced Research and Innovation Taiyuan 030032China Zhongda Hospital School of Life Sciences and TechnologyAdvanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Nanjing University Medical School Nanjing 210046China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430072China Department of Medical Molecular Biology Beijing Institute of BiotechnologyCollaborative Innovation Center for Cancer MedicineBeijing 100850China

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

关键词： endocytosis cargo uptake

Relation Between the Eventual Continuity and the E-property for Markov-Feller Semigroups

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 1-16页

作者： Yong liu Zi-yu liu LMAM School of Mathematical SciencePeking UniversityBeijing100871China

We investigate some relations between two kinds of semigroup regularities, namely the e-property and the eventual continuity, both of which contribute to the ergodicity for Markov processes on Polish spaces.More precisely, we prove that for Markov-Feller semigroup in discrete time and stochastically continuous MarkovFeller semigroup in continuous time, if there exists an ergodic measure whose support has a nonempty interior,then the e-property is satisfied on the interior of the support. In particular, it implies that, restricted on the support of each ergodic measure, the e-property and the eventual continuity are equivalent for the discrete-time and the stochastically continuous continuous-time Markov-Feller semigroups.

关键词： Markov-Feller semigroup ergodicity e-property eventual continuity

Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application

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Acta Pharmaceutica Sinica B 2024年第2期14卷 602-622页

作者： Han liu Zhiyang Wen Zihan liu Yanfang Yang Hongliang Wang Xuejun Xia Jun Ye Yuling liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic effect.Based on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used biomaterial.Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in vivo.Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination.ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing ability.Owing to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium supplementation.Emphasis in this paper has been placed on the origin,structural features,and multiple applications of ACC.Meanwhile,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these challenges.We hope that this study will contribute to future innovative research on ACC.

关键词： Amorphous calcium carbonate Drugdelivery system Nanoparticle Acid sensitivity Water instability,Tumortherapy Tissue engineering Calcium supplement

Challenges and Opportunities in Preserving Key Structural Features of 3D-Printed Metal/Covalent Organic Framework

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Nano-Micro Letters 2024年第8期16卷 362-381页

作者： Ximeng liu Dan Zhao John Wang Department of Materials Science and Engineering National University of SingaporeSingapore 117574Singapore Department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117585Singapore National University of Singapore(Chongqing)Research Institute Chongqing 401123People’s Republic of China

Metal-organic framework(MOF)and covalent organic framework(COF)are a huge group of advanced porous materials exhibiting attractive and tunable microstructural features,such as large surface area,tunable pore size,and functional surfaces,which have significant values in various application areas.The emerging 3D printing technology further provides MOF and COFs(M/COFs)with higher designability of their macrostructure and demonstrates large achievements in their performance by shaping them into advanced 3D monoliths.However,the currently available 3D printing M/COFs strategy faces a major challenge of severe destruction of M/COFs’microstructural features,both during and after 3D printing.It is envisioned that preserving the microstructure of M/COFs in the 3D-printed monolith will bring a great improvement to the related applications.In this overview,the 3D-printed M/COFs are categorized into M/COF-mixed monoliths and M/COF-covered monoliths.Their differences in the properties,applications,and current research states are discussed.The up-to-date advancements in paste/scaffold composition and printing/covering methods to preserve the superior M/COF microstructure during 3D printing are further discussed for the two types of 3D-printed M/COF.Throughout the analysis of the current states of 3D-printed M/COFs,the expected future research direction to achieve a highly preserved microstructure in the 3D monolith is proposed.

关键词： Metal-organic frameworks Covalent organic frameworks 3D printing Microstructure Monolith