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HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies

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Genes & Diseases 2024年第1期11卷 234-251页

作者： Yan Zhao Cheng Xing Yating Deng can ye Hongling Peng Department of Hematology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

The hypoxic microenvironment is an essential characteristic of most malignant ***,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via *** the intra-tumoral hypoxic environment,HIF-1αis highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in ***,it has been indicated that HiF-1αinvolves in various critical pro-cesses of life events and tumor development via regulating the expression of HiF-1a target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,*** from solid tumors,accumulating evidence has re-vealed that HiF-1αis also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple *** inhibition of HiF-1a can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic *** the review,we elaborated on the basic structure and biological functions of HIF-1a and summarized their current role in various *** is expected that they will have future potential fortargeted therapy.

关键词： Angiogenesis Hematological malignancies Hypoxia-inducible factor-1 alpha(HIF-1α) Immune escape Targeted therapy

Multi-exit self-distillation with appropriate teachers

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Frontiers of Information Technology & Electronic Engineering 2024年第4期25卷 585-599页

作者： Wujie SUN Defang CHEN can WANG Deshi ye Yan FENG Chun CHEN College of Computer Science and Technology Zhejiang UniversityHangzhou 310000China

Multi-exit architecture allows early-stop inference to reduce computational cost,which can be used in resource-constrained *** works combine the multi-exit architecture with self-distillation to simultaneously achieve high efficiency and decent performance at different network ***,existing methods mainly transfer knowledge from deep exits or a single ensemble to guide all exits,without considering that inappropriate learning gaps between students and teachers may degrade the model performance,especially in shallow *** address this issue,we propose Multi-exit self-distillation with Appropriate TEachers(MATE)to provide diverse and appropriate teacher knowledge for each *** MATE,multiple ensemble teachers are obtained from all exits with different trainable *** exit subsequently receives knowledge from all teachers,while focusing mainly on its primary teacher to keep an appropriate gap for efficient knowledge *** this way,MATE achieves diversity in knowledge distillation while ensuring learning *** results on CIFAR-100,TinyImageNet,and three fine-grained datasets demonstrate that MATE consistently outperforms state-of-the-art multi-exit self-distillation methods with various network architectures.

关键词： Multi-exit architecture Knowledge distillation Learning gap

Investigations of Water Flow Behaviors Induced by Local Temperature Variations through a Single Rough Fracture for the Enhanced Geothermal Systems

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Journal of Thermal Science 2024年第3期33卷 1055-1064页

作者： LI Jiawei ye Lin Department of Energy and Power Engineering Tsinghua UniversityBeijing100084China School of Power and Energy Northwestern Polytechnical UniversityXi’an710072China

In recent years,Enhanced Geothermal System(EGS)technologies have been applied to the geothermal resources production in the Hot Dry Rock(HDR).The core of EGS technologies is to adopt hydraulic fracturing in the reservoir to create a connected network of discrete fractures with the consideration of water as a working fluid for hydraulic fracturing and heat *** paper investigates the characteristics of water flow behaviors through a single rough fracture under different temperature and pressure conditions.A single fracture model with rough fracture surfaces is constructed and then characterized,and influences of the anisotropic factor on the average tortuosity and frictional resistance coefficient of water flow through a single fracture with rough surfaces have been compared and *** consideration of other impacting factors(temperature,pressure,fracture roughness),the impact of mass flow rate has also been *** simulation results present that changes of average tortuosity for water flow through a single rough facture are mainly affected by *** can be observed that higher temperature leads to larger average tortuosity but the frictional resistance coefficient shows an opposite *** for pressure conditions,it is found that effects of pressure on average tortuosity and frictional resistance coefficient is very small,which can be neglected under high pressure ***,the average tortuosity shows a progressively linear relationship with the mass flow *** the contrary,the frictional resistance coefficient has a negative relationship with the mass flow *** is revealed that when the mass flow rate reaches a critical point,the influences of temperature on the frictional resistance coefficient will be *** of single rough fractures with different anisotropic factors show that values of average tortuosity and frictional resistance coefficient have positive relationships with the increase

关键词： single rough fracture tortuosity frictional resistance enhanced geothermal system

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Severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

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World Journal of Pediatrics 2024年第4期20卷 307-324页

作者： Yi‑Kan Sun can Wang Pei‑Quan Lin Lei Hu Jing ye Zhi‑Gang Gao Ru Lin Hao‑Min Li Qiang Shu Li‑Su Huang Lin‑Hua Tan Children's Hospital Zhejiang University School of MedicineHangzhou 310052China The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310030China Surgical Intensive Care Unit Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of General Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiopulmonary and Extracorporeal Life Support Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Clinical Data Center Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiac Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Infectious Diseases Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in ***,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from ***,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely *** sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang *** keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated *** respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be *** immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical *** inflammatory syndrome in children(MIS-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric *** the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult *** Severe pediatric COVID-19 can affect multiple organ *** dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the

关键词： Immunopathophysiology MIS-C Pediatric critical care Severe pediatric COVID-19

Path-Dependent Progressive Failure Analysis for 3D-Printed Continuous Carbon Fibre Reinforced Composites

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Chinese Journal of Mechanical Engineering 2024年第4期37卷 84-93页

作者： Yuan Chen Lin ye School of System Design and Intelligent Manufacturing(SDIM) Southern University of Science and TechnologyShenzhen 518055China Shenzhen Key Laboratory of Intelligent Manufacturing for Continuous Carbon Fibre Reinforced Composites Southern University of Science and TechnologyShenzhen 518055China

In order to predict the damage behaviours of 3D-printed continuous carbon fibre(CCF)reinforced composites,when additional short carbon fibre(SCF)composite components are employed for continuous printing or special functionality,a novel path-dependent progressive failure(PDPF)numerical approach is ***,a progressive failure model using Hashin failure criteria with continuum damage mechanics to account for the damage initiation and evaluation of 3D-printed CCF reinforced polyamide(PA)composites is developed,based on actual fibre placement trajectories with physical measurements of 3D-printed CCF/PA ***,an elastic-plastic model is employed to predict the plastic damage behaviours of SCF/PA ***,the accuracy of the PDPF model was validated so as to study 3D-printed CCF/PA composites with either negative Poisson's ratio or high *** results demonstrate that the proposed PDPF model can achieve higher prediction accuracies in mechanical properties of these 3D-printed CCF/PA *** analyses show that the stress distribution is generally aggregated in the CCF areas along the fibre placement paths,and the shear damage and matrix tensile/compressive damage are the key damage *** study provides a new approach with valuable information for characterising complex 3D-printed continuous fibre-matrix composites with variable mechanical properties and multiple constituents.

关键词： 3D printing Continuous carbon fibre Modelling Energy absorption Negative Poisson's ratio

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Global precipitation change during the Holocene:a combination of records and simulations

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Frontiers of Earth Science 2024年第1期18卷 112-126页

作者： Wangting ye Yu LI Key Laboratory of Western China᾽s Environmental Systems(Ministry of Education) College of Earth and Environmental SciencesCenter for Hydrologic Cycle and Water Resources in Arid RegionLanzhou UniversityLanzhou 730000China

Precipitation can shape our climate both in the present and the *** though we have made significant advances in studying the mechanisms of millennial-scale climate changes through high-resolution records,we still cannot quantitatively characterize the global spatiotemporal precipitation variations within the ***,we developed a new approach to integrating data from 349 globally distributed records and climate models to reconstruct regional and global precipitation patterns over the last 12000 *** results reveal that precipitation reconstructions can be divided into monsoon-driven and westerly driven *** results suggest that an arid climate was experienced in the late glacial and early Holocene epoch(~12−7.4 cal ka BP),attaining a middle Holocene optimum(~7.4−3.5 cal ka BP),and drier after the middle *** to our reconstructions,the global precipitation reconstruction increased from the early Holocene until 3.8 cal ka BP and then subsequently *** addition,our reconstructions better reproduce the low-frequency events and extreme precipitation at the millennial scale in the hemispheres,but the performance of the reconstructions in the equatorial Pacific and the Southern Hemisphere of Africa and the Americas is *** resolution of the record and the simulation capability of the climate model remain important means to improve our understanding of past climate change.

关键词： Holocene equatorial glacial

A novel relationship between elastic modulus and void ratio associated with principal stress for coral calcareous sand

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第3期16卷 1033-1048页

作者： Ran Gao Jianhong ye State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China

Elastic moduli,*** modulus G and bulk modulus K,are important parameters of geotechnical materials,which are not only the indices for the evaluation of the deformation ability of soils but also the important basic parameters for the development of the constitutive models of geotechnical *** this study,a series of triaxial loading-unloading-reloading shear tests and isotropic loading-unloadingreloading tests are conducted to study several typical mechanical properties of coral calcareous sand(CCS),and the void ratio evolution during loading,unloading and *** test results show that the stress-strain curves during multiple unloading processes are almost parallel,and their slopes are much greater than the deformation modulus at the initial stage of *** relationship between the confining pressure and the volumetric strain can be defined approximately by a hyperbolic equation under the condition of monotonic loading of confining *** the condition of confining pressure unloading,the evolution of void ratio is linear in the e-lnp0 plane,and these lines are a series of almost parallel lines if there are multiple processes of *** on the experimental results,it is found that the modified Hardin formulae for the elastic modulus estimation have a significant deviation from the tested values for *** on the experimental results,it is proposed that the elastic modulus of soils should be determined by the intersection line of two spatial surfaces in the G/K-e-p’/pa space(pa:atmosphere pressure).“ye formulation”is further proposed for the estimation of the elastic modulus of *** new estimation formulation for soil elastic modulus would provide a new method to accurately describe the mechanical behavior of granular soils.

关键词： Coral calcareous sand(CCS) Elastic shear modulus Elastic bulk modulus Triaxial test Estimation formulation ye formulation

General formalism for dirty extreme-mass-ratio inspirals

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 22-29页

作者： ye Jiang Wen-Biao Han Shanghai Astronomical Observatory Chinese Academy of SciencesShanghai 200030China School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Shanghai Frontiers Science Center for Gravitational Wave Detection Shanghai 200240China

Detecting the environment around the supermassive black holes and tests of general relativity are important applications of extreme-mass-ratio inspirals(EMRIs).There is still a challenge to efficiently describe various“dirty”impacts on the inspirals,such as dark matter,gas,dipole radiation,and electromagnetic *** this study,we find the inherent linearity of the asymptotic solution of the inhomogeneous Teukolsky *** the basis of this property,we completely decouple the factors of the perturber and the background spacetime in the energy fluxes and *** the new decoupling form,the waveforms of EMRIs with non-geodesic motion in Kerr spacetime can be conveniently *** will help to resolve the environment(including gas,field,dark matter,electromagnetic interaction)around supermassive black holes and test general relativity.

关键词： gravitational wave Teukolsky equation extreme-mass-ratio inspirals

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Finite Element Simulation Analysis of a Novel 3D-FRSPA for Crawling Locomotion

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1401-1425页

作者： Bingzhu Wang Xiangrui ye College of Mechanics and Materials Hohai UniversityNanjing211100China Department of Fundamental Ma’anshan UniversityMa’anshan243100China

A novel three-dimensional-fiber reinforced soft pneumatic actuator(3D-FRSPA)inspired by crab claw and human hand structure that can bend and deform independently in each segment is *** has an omni-directional bending configuration,and the fibers twined symmetrically on both sides to improve the bending performance of *** this paper,the static and kinematic analysis of 3D-FRSPA are carried out in *** effects of fiber,pneumatic chamber and segment length,and circular air chamber radius of 3D-FRSPA on the mechanical performance of the actuator are discussed,*** soft mobile robot composed of 3D-FRSPA has the ability to ***,the crawling processes of the soft mobile robot on different road conditions are studied,respectively,and the motion mechanism of the mobile actuator is *** numerical results show that the soft mobile robots have a good comprehensive performance,which verifies the correctness of the *** work shows that the proposed structures have great potential in complex road conditions,unknown space detection and other operations.

关键词： 3D-FRSPA bionic structure theoretical modeling crawling application obstacle avoidance analysis numerical investigation