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Carbonic anhydrase-like enzymes in the formation of Lycopodium alkaloid

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Chinese Journal of Natural Medicines 2024年第3期22卷 193-194页

作者： dong Huiwen GE Huiming State key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China

Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the discovery of new natural products and pathways.It may also shed light on the roles of existing pathways in host biology and provide valuable tools for metabolic engineering in plants and microbes[2].Unlike other major classes of plant natural products,such as terpenoids and polyketides,the formation of alkaloid scaffolds does not conform to a uniform chemical theme or depend on a singular enzyme class[3].A case in point is the Lycopodium alkaloids in the Lycopodiaceae family,where the enzymes responsible for their core scaffold construction remain unidentified[4].

关键词： Lycopodium alkaloid Carbonic anhydrase-like enzymes Biosynthesis

Towards full-stack deep learning-empowered data processing pipeline for synchrotron tomography experiments

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The Innovation 2024年第1期5卷 127-138页

作者： Zhen Zhang Chun Li Wenhui Wang Zheng dong Gongfa Liu Yuhui dong Yi Zhang National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China Beijing Synchrotron Radiation Facility Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China

Synchrotron tomography experiments are transitioning into multifunctional,cross-scale,and dynamic characterizations,enabled by new-generation synchrotron light sources and fast developments in beamline instrumentation.However,with the spatial and temporal resolving power entering a new era,this transition generates vast amounts of data,which imposes a significant burden on the data processing end.Today,as a highly accurate and efficient data processing method,deep learning shows great potential to address the big data challenge being encountered at future synchrotron beamlines.In this review,we discuss recent advances employing deep learning at different stages of the synchrotron tomography data processing pipeline.We also highlight how applications in other data-intensive fields,such as medical imaging and electron tomography,can be migrated to synchrotron tomography.Finally,we provide our thoughts on possible challenges and opportunities as well as the outlook,envisioning selected deep learning methods,curated big models,and customized learning strategies,all through an intelligent scheduling solution.

关键词： processing pipeline outlook

Current understanding of ELF4 deficiency:a novel inborn error of immunity

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World Journal of Pediatrics 2024年第5期20卷 444-450页

作者： Hong-Qiang Du Xiao-dong Zhao Department of Rheumatology&Immunology National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityZhongshan Er Road 136Yuzhong DistrictChongqingChina

Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

关键词： ELF4 transcription factor Immune dysregulation Inborn errors of immunity Mechanism Recurrent infections

A Long-Time-Step-Permitting Tracer Transport Model on the Regular Latitude–Longitude Grid

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Advances in Atmospheric Sciences 2024年第3期41卷 493-508页

作者： Jianghao LI Li dong Key Laboratory of Earth System Modeling and Prediction China Meteorological AdministrationBeijing 100081China State key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics(LASG) Institute of Atmospheric Physics(IAP)Chinese Academy of SciencesBeijing 100029China State Key Laboratory of Severe Weather(LaSW) Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081China College of Earth and Planetary Sciences University of Chinese Academy of SciencesBeijing 100049China

If an explicit time scheme is used in a numerical model, the size of the integration time step is typically limited by the spatial resolution. This study develops a regular latitude–longitude grid-based global three-dimensional tracer transport model that is computationally stable at large time-step sizes. The tracer model employs a finite-volume flux-form semiLagrangian transport scheme in the horizontal and an adaptively implicit algorithm in the vertical. The horizontal and vertical solvers are coupled via a straightforward operator-splitting technique. Both the finite-volume scheme's onedimensional slope-limiter and the adaptively implicit vertical solver's first-order upwind scheme enforce monotonicity. The tracer model permits a large time-step size and is inherently conservative and monotonic. Idealized advection test cases demonstrate that the three-dimensional transport model performs very well in terms of accuracy, stability, and efficiency. It is possible to use this robust transport model in a global atmospheric dynamical core.

关键词： tracer transport numerical stability latitude–longitude grid

CONVERGENCE ANALYSIS OF SOME FINITE ELEMENT PARALLEL ALGORITHMS FOR THE STATIONARY INCOMPRESSIBLE MHD EQUATIONS

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Journal of Computational Mathematics 2024年第1期42卷 49-70页

作者： Xiaojing dong Yinnian He Hunan Key Laboratory for Computation and Simulation in Science and Engineering Key Laboratory of Intelligent Computing&Information Processing of Ministry of EducationSchool of Mathematics and Computational ScienceXiangtan UniversityXiangtan 411105China Institute of Applied Physics and Computational Mathematics Beijing 100088China School of Mathematics and Statistics Xi'an Jiaotong UniversityXi'an 710049China

By combination of iteration methods with the partition of unity method(PUM),some finite element parallel algorithms for the stationary incompressible magnetohydrodynamics(MHD)with different physical parameters are presented and analyzed.These algorithms are highly efficient.At first,a global solution is obtained on a coarse grid for all approaches by one of the iteration methods.By parallelized residual schemes,local corrected solutions are calculated on finer meshes with overlapping sub-domains.The subdomains can be achieved flexibly by a class of PUM.The proposed algorithm is proved to be uniformly stable and convergent.Finally,one numerical example is presented to confirm the theoretical findings.

关键词： Partition of unity method Local and parallel algorithm Finite element method Iteration methods Magnetohydrodynamics

Numerical Investigations on the Resonance Errors of Multiscale Discontinuous Galerkin Methods for One-Dimensional Stationary Schrödinger Equation

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Communications on Applied Mathematics and Computation 2024年第1期6卷 311-324页

作者： Bo dong Wei Wang Department of Mathematics University of Massachusetts DartmouthNorth DartmouthMA02747USA Department of Mathematics and Statistics Florida International UniversityMiamiFL33199USA

In this paper,numerical experiments are carried out to investigate the impact of penalty parameters in the numerical traces on the resonance errors of high-order multiscale discontinuous Galerkin(DG)methods(dong et al.in J Sci Comput 66:321–345,2016;dong and Wang in J Comput Appl Math 380:1–11,2020)for a one-dimensional stationary Schrödinger equation.Previous work showed that penalty parameters were required to be positive in error analysis,but the methods with zero penalty parameters worked fine in numerical simulations on coarse meshes.In this work,by performing extensive numerical experiments,we discover that zero penalty parameters lead to resonance errors in the multiscale DG methods,and taking positive penalty parameters can effectively reduce resonance errors and make the matrix in the global linear system have better condition numbers.

关键词： Discontinuous Galerkin(DG)method Multiscale method Resonance errors One-dimensional Schrödinger equation

MicroR-9c-5p and novel-mir50 co-target Akt to regulate Lasioderma serricorne reproduction

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Insect Science 2024年第1期31卷 106-118页

作者： Yi Yan dong-dong Qin Hong Yang Kang-Kang Xu Can Li Wen-Jia Yang Provincial Key Laboratory for Agricultural Pest Management of Mountainous Region Institute of EntomologyGuizhou UniversityGuiyangChina Guizhou Provincial Key Laboratory for Rare Animal and Economic Insect of the Mountainous Region College of Biology and Environmental EngineeringGuiyang UniversityGuiyangChina

High fecundity is a common characteristic of insect pests which increases the difficulty of population control.Serine/threonine kinase Akt is an indispensable component of the insulin signaling pathway.Silencing of LsAkt severely hinders reproduction in Lasioderma serricorne,a stored product insect pest.However,the post-transcriptional pathway of LsAkt in L.serricorne remains unknown.This study identified 2 binding sites of miR-9c-5p and novel-mir50 in the coding sequences of LsAkt.The expression profiles of 2 microRNAs(miRNAs)and LsAkt displayed an opposite pattern during the adult stages.Luciferase reporter assay showed that novel-mir50 and miR-9c-5p could downregulate the expression of LsAkt.Overexpression of miR-9c-5p and novel-mir50 by injection of mimics inhibited the expression of LsAkt and reduced oviposition,decreased egg hatchability,and blocked ovarian development.It also decreased the expression of genes involved in ovarian development(LsVg and LsVgR)and the nutritional signaling pathway(LsTOR,LsS6K,and Ls4EBP),and reduced the phosphorylation of Akt.Conversely,injection of miR-9c-5p and novel-mir50 inhibitors induced the expressions of LsAkt,LsVg,LsVgR,LsTOR,LsS6K,and Ls4EBP,enhanced Akt phosphorylation level,and accelerated ovarian development.Injection of bovine insulin downregulated the expression of miR-9c-5p and novel-mir50 and upregulated the LsAkt expression.It also rescued the reproductive development defects associated with miR-9c-5p/novel-mir50 overexpression,forming a positive regulatory loop of insulin signaling.These results indicate that miR-9c-5p/novel-mir50 regulates the female reproduction of L.serricorne by targeting Akt in response to insulin signaling.The data also demonstrate the effects of the insulin/miRNA/Akt regulatory axis in insect reproduction.

关键词： Akt insulin Lasioderma serricorne microRNA reproduction

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-dong Qin Xiao-dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each other.Due to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol framework.In recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities.Despite the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains limited.The majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs.Therefore,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision medicine.Meanwhile,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

A New Method for Solving Nonlinear Partial Differential Equations Based on Liquid Time-Constant Networks

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Journal of Systems Science & Complexity 2024年第2期37卷 480-493页

作者： SUN Jiuyun dong Huanhe FANG Yong College of Mathematics and Systems Science Shandong University of Science and TechnologyQingdao 266590China

In this paper,physics-informed liquid networks(PILNs)are proposed based on liquid time-constant networks(LTC)for solving nonlinear partial differential equations(PDEs).In this approach,the network state is controlled via ordinary differential equations(ODEs).The significant advantage is that neurons controlled by ODEs are more expressive compared to simple activation functions.In addition,the PILNs use difference schemes instead of automatic differentiation to construct the residuals of PDEs,which avoid information loss in the neighborhood of sampling points.As this method draws on both the traveling wave method and physics-informed neural networks(PINNs),it has a better physical interpretation.Finally,the KdV equation and the nonlinear Schr¨odinger equation are solved to test the generalization ability of the PILNs.To the best of the authors’knowledge,this is the first deep learning method that uses ODEs to simulate the numerical solutions of PDEs.

关键词： Nonlinear partial differential equations numerical solutions physics-informed liquid networks physics-informed neural networks