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A mutation in TBXT causes congenital vertebral malformations in humans and mice

Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen Yunping Lei Yajun Yang Chennan Liu lele kuang Li Jin Richard HFinnell Xueyan Yang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM *** heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation

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Rare variants in TULP3 abolish the suppressive effect on sonic hedgehog signaling and contribute to human neural tube defects

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Genes & Diseases 2022年第5期9卷 1174-1177页

作者： lele kuang Yuchao Jiang Shuxia Chen Ke Su Rui Peng Xueyan Yang Hongyan Wang Obstetrics and Gynecology Hospital NHC Key Laboratory of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research)Children's HospitalFudan UniversityShanghai 200011PR China Department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092PR China The MOE Key Laboratory of Contemporary Anthropology Department of Anthropology and Human GeneticsSchool of Life SciencesFudan UniversityShanghai 200438PR China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Institute of Metabolism and Integrative BiologyInstitute of Reproduction and DevelopmentInstitutes of Biomedical SciencesFudan UniversityShanghai 200090PR China

To the Editor:Neural tube defects(NTDs)are among the most common human birth defects affecting about 1/1000 live births worldwide.1 The etiology of NTDs is attributed to complex genetic and environmental risk *** 200 genes have been identified to cause NTDs in animal models,suggesting the involvement of distinct molecular basis in NTD etiology,including the Sonic hedgehog(Shh)signaling.

关键词： involvement neural attributed

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Inter-well internal resonance analysis of rectangular asymmetric cross-ply bistable composite laminated cantilever shell under transverse foundation excitation

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Applied Mathematics and Mechanics(English Edition) 2024年第8期45卷 1353-1373页

作者： lele REN Wei ZHANG Yufei ZHANG State Key Laboratory of Mechanical System and Vibration Shanghai Jiao Tong University Department of Mechanics Guangxi University Beijing Key Laboratory of Nonlinear Vibrations and Strength of Mechanical Structures College of Mechanical Engineering Beijing University of Technology

The chaotic dynamic snap-through and complex nonlinear vibrations are investigated in a rectangular asymmetric cross-ply bistable composite laminated cantilever shell, in cases of 1 : 2 inter-well internal resonance and primary resonance. The transverse foundation excitation is applied to the fixed end of the structure, and the other end is in a free state. The first-order approximate multiple scales method is employed to perform the perturbation analysis on the dimensionless two-degree-of-freedom ordinary differential motion control equation. The four-dimensional averaged equations are derived in both polar and rectangular coordinate forms. Deriving from the obtained frequency-amplitude and force-amplitude response curves, a detailed analysis is conducted to examine the impacts of excitation amplitude, damping coefficient, and tuning parameter on the nonlinear internal resonance characteristics of the system. The nonlinear softening characteristic is exhibited in the upper stable-state, while the lower stable-state demonstrates the softening and linearity characteristics. Numerical simulation is carried out using the fourth-order Runge-Kutta method, and a series of nonlinear response curves are plotted. Increasing the excitation amplitude further elucidates the global bifurcation and chaotic dynamic snap-through characteristics of the bistable cantilever shell.

关键词： 74K10 bistable composite laminated cantilever shell chaotic dynamic snap-through complex nonlinear vibration inter-well internal resonance O322 primary resonance

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Black Phosphorus for Photonic Integrated Circuits

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Research 2024年第2期2023卷 339-353页

作者： Mingxin Zhang lele Yang Xiaoxuan Wu Junjia Wang National Research Center for Optical Sensors/communications Integrated Networks School of Electronic Science and EngineeringSoutheast University2 SipailouNanjing 210096China

Black phosphorus gives several advantages and complementarities over other two-dimensional *** has drawn extensive interest owing to its relatively high carrier mobility,wide tunable bandgap,and in-plane anisotropy in recent *** manuscript briefly reviews the structure and physical properties of black phosphorus and targets on black phosphorus for photonic integrated *** of the applications are discussed including photodetection,optical modulation,light emission,and polarization *** recent progresses,associated challenges,and future potentials are covered.

关键词： polarization tunable phosphorus

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Combination strategies for first-line treatment of patients with unresectable hepatocellular carcinoma:prospect of natural products

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Chinese Journal of Natural Medicines 2024年第1期22卷 1-3页

作者： ZHANG lele LU Jinjian School of Basic Medical Sciences Chengdu UniversityChengdu 610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical ***,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

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Snap-through behaviors and nonlinear vibrations of a bistable composite laminated cantilever shell:an experimental and numerical study

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Applied Mathematics and Mechanics(English Edition) 2024年第5期45卷 779-794页

作者： lele REN Wei ZHANG Ting DONG Yufei ZHANG State Key Laboratory of Mechanical System and Vibration Shanghai Jiao Tong UniversityShanghai 200240China Department of Mechanics Guangxi UniversityNanning 530004China Beijing Key Laboratory of Nonlinear Vibrations and Strength of Mechanical Structures College of Mechanical EngineeringBeijing University of TechnologyBeijing 100124China School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China

The snap-through behaviors and nonlinear vibrations are investigated for a bistable composite laminated cantilever shell subjected to transversal foundation excitation based on experimental and theoretical *** improved experimental specimen is designed in order to satisfy the cantilever support boundary condition,which is composed of an asymmetric region and a symmetric *** symmetric region of the experimental specimen is entirely clamped,which is rigidly connected to an electromagnetic shaker,while the asymmetric region remains free of *** motion paths are realized for the bistable cantilever shell by changing the input signal levels of the electromagnetic shaker,and the displacement responses of the shell are collected by the laser displacement *** numerical simulation is conducted based on the established theoretical model of the bistable composite laminated cantilever shell,and an off-axis three-dimensional dynamic snap-through domain is *** numerical solutions are in good agreement with the experimental *** nonlinear stiffness characteristics,dynamic snap-through domain,and chaos and bifurcation behaviors of the shell are quantitatively *** to the asymmetry of the boundary condition and the shell,the upper stable-state of the shell exhibits an obvious soft spring stiffness characteristic,and the lower stable-state shows a linear stiffness characteristic of the shell.

关键词： bistable composite laminated cantilever shell snap-through behavior nonlinear vibration nonlinear stiffness characteristic chaos and bifurcation

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Indentation behavior of a semi-infinite piezoelectric semiconductor under a rigid flat-ended cylindrical indenter

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 649-662页

作者： Shijing GAO lele ZHANG Jinxi LIU Guoquan NIE Weiqiu CHEN State Key Laboratory of Mechanical Behavior and System Safety of Traffic Engineering Structures Shijiazhuang Tiedao UniversityShijiazhuang 050043China School of Mechanical Engineering Shijiazhuang Tiedao UniversityShijiazhuang 050043China Hebei Key Laboratory for Mechanics of Intelligent Materials and Structures Department of Engineering MechanicsShijiazhuang Tiedao UniversityShijiazhuang 050043China State Key Laboratory of Computer Aided Design and Computer Graphics Key Laboratory of Soft Machines and Smart Devices of Zhejiang ProvinceDepartment of Engineering MechanicsZhejiang UniversityHangzhou 310027China

This paper theoretically studies the axisymmetric frictionless indentation of a transversely isotropic piezoelectric semiconductor(PSC)half-space subject to a rigid flatended cylindrical *** contact area and other surface of the PSC half-space are assumed to be electrically *** the Hankel integral transformation,the problem is reduced to the Fredholm integral equation of the second *** equation is solved numerically to obtain the indentation behaviors of the PSC half-space,mainly including the indentation force-depth relation and the electric potential-depth *** results show that the effect of the semiconductor property on the indentation responses is limited within a certain range of variation of the steady carrier *** dependence of indentation behavior on material properties is also analyzed by two different kinds of *** element simulations are conducted to verify the results calculated by the integral equation technique,and good agreement is demonstrated.

关键词： piezoelectric semiconductor(PSC) insulating indenter electromechanical response singular integral equation finite element simulation

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Convolutional neural network adaptation and optimization method in SIMT computing mode

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The Journal of China Universities of Posts and Telecommunications 2024年第2期31卷 105-112页

作者： Feng Zhenfu Zhang Yaying Yang lele Xing Lidong School of Electronic Engineering Xi'an University of Posts and TelecommunicationsXi'an 710121China

For studying and optimizing the performance of general-purpose computing on graphics processing units(GPGPU)based on single instruction multiple threads(SIMT)processor about the neural network application,this work contributes a self-developed SIMT processor named Pomelo and correlated assembly *** parallel mechanism of SIMT computing mode and self-developed Pomelo processor is briefly introduced.A common convolutional neural network(CNN)is built to verify the compatibility and functionality of the Pomelo *** computing flow with task level and hardware level optimization is adopted on the Pomelo processor.A specific algorithm for organizing a Z-shaped memory structure is developed,which addresses reducing memory access in mass data computing *** the above-combined adaptation and optimization strategy,the experimental result demonstrates that reducing memory access in SIMT computing mode plays a crucial role in improving performance.A 6.52 times performance is achieved on the 4 processing elements case.

关键词： parallel computing single instruction multiple threads(SIMT) convolutional neural network(CNN) memory optimization

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New insights into the pre-lithiation kinetics of single-crystalline Ni-rich cathodes for long-life Li-ion batteries

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Green Energy & Environment 2024年第3期9卷 556-564页

作者： Qiang Han lele Cai Zhaofeng Yang Yanjie Hu Hao Jiang Chunzhong Li Shanghai Engineering Research Center of Hierarchical Nanomaterials School of Chemical EngineeringEast China University of Science and TechnologyShanghai200237China Key Laboratory for Ultrafine Materials of Ministry of Education School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China

Developing single-crystalline Ni-rich cathodes is an effective strategy to improve the safety and cycle life of Li-ion batteries(LIBs).However,the easy-to-loss of Li and O in high-temperature lithiation results in unsatisfactory ordered layered structure and ***,we demonstrate the synthesis of highly-ordered and fully-stoichiometric single-crystalline LiNi_(0.83)Co_(0.12)Mn_(0.05)O_(2)(SC-NCM83)cathodes by the regulation of pre-lithiation *** well-balanced pre-lithiation kinetics have been proved to greatly improve the proportion of layered phase in the intermediate by inhibiting the formation of metastable spinel phase,which promoted the rapid transformation of the intermediate into highly-ordered layered SC-NCM83 in the subsequent lithiation *** coating a layer of Li_(2)O–B_(2)O_(3),the resultant cathodes deliver superior cycling stability with 90.9%capacity retention at 1C after 300 cycles in pouch-type full *** enhancement mechanism has also been *** findings exhibit fundamental insights into the pre-lithiation kinetics process for guiding the synthesis of high-quality singlecrystalline Ni-rich cathodes.

关键词： Single-crystalline cathode Ni-rich oxides Pre-lithiation Li-ion batteries Surface modification

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Quantification of the concrete freeze–thaw environment across the Qinghai–Tibet Plateau based on machine learning algorithms

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Journal of Mountain Science 2024年第1期21卷 322-334页

作者： QIN Yanhui MA Haoyuan ZHANG lele YIN Jinshuai ZHENG Xionghui LI Shuo Department of Civil Engineering Qingdao University of TechnologyQingdao 266520China Department of Geography Qinghai Normal UniversityXining 810008China

The reasonable quantification of the concrete freezing environment on the Qinghai–Tibet Plateau(QTP) is the primary issue in frost resistant concrete design, which is one of the challenges that the QTP engineering managers should take into account. In this paper, we propose a more realistic method to calculate the number of concrete freeze–thaw cycles(NFTCs) on the QTP. The calculated results show that the NFTCs increase as the altitude of the meteorological station increases with the average NFTCs being 208.7. Four machine learning methods, i.e., the random forest(RF) model, generalized boosting method(GBM), generalized linear model(GLM), and generalized additive model(GAM), are used to fit the NFTCs. The root mean square error(RMSE) values of the RF, GBM, GLM, and GAM are 32.3, 4.3, 247.9, and 161.3, respectively. The R^(2) values of the RF, GBM, GLM, and GAM are 0.93, 0.99, 0.48, and 0.66, respectively. The GBM method performs the best compared to the other three methods, which was shown by the results of RMSE and R^(2) values. The quantitative results from the GBM method indicate that the lowest, medium, and highest NFTC values are distributed in the northern, central, and southern parts of the QTP, respectively. The annual NFTCs in the QTP region are mainly concentrated at 160 and above, and the average NFTCs is 200 across the QTP. Our results can provide scientific guidance and a theoretical basis for the freezing resistance design of concrete in various projects on the QTP.

关键词： Freeze–thaw cycles Quantification Machine learning algorithms Qinghai–Tibet Plateau Concrete

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