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Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

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Oncology Research 2024年第6期32卷 1119-1128页

作者： YUE ZHANG wenyu YANG XIAOWANG HAN YUE QIAO HAITAO WANG TING CHEN TIANYING LI WEN-BIN OU Department of Biopharmaceutics College of Life Sciences and MedicineZhejiang Provincial Key Laboratory of Silkworm Bioreactor and BiomedicineZhejiang Sci-Tech UniversityHangzhou310018China Department of Thoracic Surgery Zhejiang Provincial People’s HospitalHangzhou310014China

It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still *** current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer genome Atlas(TCGA)*** HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and ***4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK *** first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative ***,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in *** findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

关键词： Lung adenocarcinoma Human epididymis protein 4 Epidermal growth factor receptor Biomarker Targeted therapies

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Preparation and Structure-Property Regulation Mechanism of Reversible Thermochromic Polydiacetylene

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Chinese Journal of Polymer Science 2024年第8期42卷 1111-1121页

作者： Zhi-Qing ge Shuo Yan Zu-Xiong Pan Shan Lei Xuan-Zhi Mao Chu Zhao Mo-Zhen Wang Xue-Wu ge Key Laboratory of Precision and Intelligent Chemistry Department of Polymer Science and EngineeringUniversity of Science and Technology of ChinaHefei 230026China Marshall Laboratory of Biomedical Engineering International Cancer CenterLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringShenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China University of Chinese Academy of Sciences Beijing 100049China

The thermochromic mechanism and the structure-property regulation principle of reversible thermochromic polydiacetylene(PDA)materials have always been a challenging *** this work,a series of diacetylene monomers(m-PCDA)containing phenyl and amide or carboxyl groups were synthesized from 10,12-pentacosadiynoic acid(PCDA)through the esterification or amidation *** effects of the number and the distribution of the functional groups in m-PCDA molecules on their solid-state polymerization capability,and the thermochromic mechanism of their corresponding polymers(m-PDA)were investigated and discussed in *** results show that the m-PCDA monomers containing both benzene ring and groups that can form hydrogen bonding interactions have strong intermolecular interaction,and are easy to carry out the solid phase polymerization under 254-nm UV irradiation to obtain the corresponding new thermochromic m-PDA *** thermochromic behavior of m-PDA depends on its melting *** initial color-change temperature(blue to red)is determined by the onset melting tem perature,and the temperature range in which reversible color recovery can be achieved by repeat heating-cooling treatment is determined by its melting *** to the proposed thermochromic mechanism of PDA,various new PDA materials with precise thermochromic temperatu res and reversible thermochromic temperature ra nges can be designed and synthesized through the appropriate introduction of benzene ring and groups that can form hydrogen bonding interactions into the molecular structure of linear diacetylene *** work provides a perspective to the precise molecular structure design and the property regulation of the reversible thermochromic PDA materials.

关键词： Polydiacetylene Thermochromism Hydrogen bonding Chemical modification

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A probabilistic generative model for tracking multi-knowledge concept mastery probability

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Frontiers of Computer Science 2024年第3期18卷 155-170页

作者： Hengyu LIU Tiancheng ZHANG Fan LI Minghe YU ge YU School of Computer Science and Engineering Northeastern UniversityShenyang 110169China Software College Northeastern UniversityShenyang 110169China

Knowledge tracing aims to track students’knowledge status over time to predict students’future performance *** a real environment,teachers expect knowledge tracing models to provide the interpretable result of knowledge *** chain-based knowledge tracing(MCKT)models,such as Bayesian Knowledge Tracing,can track knowledge concept mastery probability over ***,as the number of tracked knowledge concepts increases,the time complexity of MCKT predicting student performance increases exponentially(also called explaining away problem).When the number of tracked knowledge concepts is large,we cannot utilize MCKT to track knowledge concept mastery probability over *** addition,the existing MCKT models only consider the relationship between students’knowledge status and problems when modeling students’responses but ignore the relationship between knowledge concepts in the same *** address these challenges,we propose an inTerpretable pRobAbilistiC generative moDel(TRACED),which can track students’numerous knowledge concepts mastery probabilities over *** solve explain away problem,we design long and short-term memory(LSTM)-based networks to approximate the posterior distribution,predict students’future performance,and propose a heuristic algorithm to train LSTMs and probabilistic graphical model *** better model students’exercise responses,we proposed a logarithmic linear model with three interactive strategies,which models students’exercise responses by considering the relationship among students’knowledge status,knowledge concept,and *** conduct experiments with four real-world datasets in three knowledge-driven *** experimental results show that TRACED outperforms existing knowledge tracing methods in predicting students’future performance and can learn the relationship among students,knowledge concepts,and problems from students’exercise *** also conduct several case *** case studies show that

关键词： probabilistic graphical model deep learning knowledge tracing learner modeling

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Advances in understanding and managing celiac disease:Pathophysiology and treatment strategies

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World Journal of Gastroenterology 2024年第35期30卷 3932-3941页

作者： Hao-Jie ge Xu-Lin Chen Department of Burns The First Affiliated Hospital of Anhui Medical UniversityHefei 230022Anhui ProvinceChina

In this editorial,we comment on an article published in the recent issue of the World Journal of *** disease(CeD)is a disease occurring in genetically susceptible individuals,which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain,diarrhea,and ***,patients often need a lifelong gluten-free diet,which greatly affects the quality of life and expenses of *** gold standard for diagnosis is intestinal mucosal biopsy,combined with serological and genetic *** present,the lack of safe,effective,and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis,and it is difficult to find a perfect target to solve the multi-level needs of *** this editorial,we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.

关键词： Celiac disease Gluten-free diet Pathology Human leukocyte antigen Immunotherapy Treatment Aspergillus niger prolyl endoprotease

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Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein(RNP)to inhibit herpes simplex virus1 infection in vitro and in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1362-1379页

作者： Yuanda Wan Liren Li Ruilin Chen Jiajia Han Qiyun Lei Zhipeng Chen Xiaodong Tang wenyu Wu Shuwen Liu Xingang Yao NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center of Clinical Pharmacy Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Key Laboratory of Infectious Diseases Research in South China(Southern Medical University) Ministry of EducationGuangzhou 510515China

Extracellular vesicles(EVs)have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins(RNPs),owing to their ability to minimize off-target effects and immune ***,enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within *** response,we employed the Fc/Spa interaction system,in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV ***,the B domain of the Spa protein was fused to the C domain of cargos such as Cre or *** to the robust interaction between Fc and Spa,this method enriched nearly twice the amount of cargo within the *** loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in ***,following neuron-targeting peptide RVG modification,the in vivo dosage in neural tissues substantially increased,contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target *** findings establish a robust platform for efficient EV-based SpCas9 delivery,offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

关键词： Extracellular vesicles CRISPR/Cas9 Ribonucleoproteins PTGFRN Fc/Spa HSV1 Neuron-targeting Delivery

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Progress in Research on Structural Ceramic Materials Toughened by Graphene

Expert Review of Chinese Chemical

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Expert Review of Chinese Chemical 2024年第2期2卷 37-42页

作者： wenyu Yao Yalong Zhang College of Materials Science and Engineering Shenyang University of Architecture

Graphene has excellent mechanical properties and unique physical/chemical properties,which make it have a good strengthening and toughening effect on structural ceramic *** recent years,it has received widespread attention and *** article reviews the mixing and sintering processes in the preparation of graphene/ceramic com-posites,as well as the toughening mechanism of graphene on ceramic *** also looks forward to how to further enhance the toughening effect of graphene.

关键词： graphene ceramics mixing materials sintering toughening

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Role of Vickers Ligament in the Pathogenesis of Madelung Deformity

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当代医学科学（英文） 2024年第4期44卷 735-740页

作者： ge XIONG Wei ZHENG Li-hua GONG Department of Hand Surgery Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Department of Pathology Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China

Objective:The Vickers ligament is thought to hinder the growth of palmar ulnar radius by tethering the lunate to the radius,leading to Madelung *** purpose of this study was to clarify the nature of the Vickers ligament and investigate its pathogenesis in Madelung deformities based on our observation of the Vickers ***:All 22 patients(33 wrists)with Madelung deformities treated surgically between 2018 and 2022 were *** diagnosis was confirmed radiographically in all *** three-dimensional computed tomography(3D-CT)data of 16 patients(19 wrists)were *** resonance imaging(MRI)data were available for 9 patients(14 wrists).Wrist arthroscopy was used in 4 *** Vickers ligament was resected and submitted for histopathological examination in 8 *** outcomes,3D-CT,MRI,arthroscopy,surgical findings,and histopathology of the Vickers ligament were ***:The 3D-CT revealed that the Vickers ligament originated in the metaphysis and formed a metaphyseal defect at the palmar ulnar *** the sequential MR coronal images,the Vickers ligament could be divided into 3 branches,extending to the lunate,triquetrum and ulnar *** and surgical findings revealed that the nature of the Vickers ligament was the stretched palmar ligament of the *** histopathology results revealed ligamentous tissue and fibrocartilaginous metaplasia with a structure similar to that of the triangular fibrocartilage complex(TFCC).Conclusions:The Vickers ligament is not a separate aberrant *** nature of the Vickers ligament is a combination of the stretched TFCC ligament(palmar radioulnar ligament,ulnotriquetral ligament and ulnolunate ligament)and radiolunate *** possible pathogenesis of Madelung deformity might be focal early epiphyseal closure at the middle part of the sigmoid notch,which leads to focal growth retardation of the radius and pulls palmar ligaments proximally to for

关键词： Madelung deformity Vickers ligament computed tomography magnetic resonance imaging pathogenesis

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Cobalt(Ⅲ)hydride HAT mediated enantioselective intramolecular hydroamination access to chiral pyrrolidines

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Science China Chemistry 2024年第6期67卷 2002-2008页

作者： Qi Meng Tao Qin Huanran Miao ge Zhang Qian Zhang Jilin Province Key Laboratory of Organic Functional Molecular Design&Synthesis Department of ChemistryNortheast Normal UniversityChangchun130024China State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai200032China

Enantioenriched pyrrolidines and derivatives are ubiquitous substructures in compounds of importance to medicinal and biological ***,we report an efficient cobalt-catalyzed intramolecular asymmetric hydroamination reaction that produces chiral pyrrolidines with good to excellent yield and *** with previously reported radicalinvolved methodologies for enantioenriched pyrrolidines,these conditions feature two elegant versatilities,enabling(1)the use of cobalt-catalyzed hydrogen atom transfer(HAT)to generate organocobalt intermediates that bring radical reaction to organometallic chemistry,and(2)enantioselective intramolecular C-N bond forging through an S_(N)2-like displacement involving dynamic kinetic resolution(DKR).This approach provides a new alternative and efficient methodology for enantioselective radical-involved C-N bond construction that can be used in the synthesis of both chiral pyrrolidines and homologous nitrogen heterocycles.

关键词： asymmetric catalysis radical hydroamination cobalt catalysis hydrogen atom transfer

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Robust fixed-time flight controller for a dual-system convertible UAV in the cruise mode

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Defence Technology 2024年第09期 53-66页

作者： Lulu Chen Zhenbao Liu Qingqing Dang Wen Zhao wenyu Chen School of Civil Aviation Northwestern Polytechnical University Shenzhen Research Institute of Northwestern Polytechnical University Air and Missile Defense College Air Force Engineering University

This paper investigates the attitude tracking control problem for the cruise mode of a dual-system convertible unmanned aerial vehicle(UAV) in the presence of parameter uncertainties, unmodeled uncertainties and wind disturbances. First, a fixed-time disturbance observer(FXDO) based on the bi-limit homogeneity theory is designed to estimate the lumped disturbance of the convertible UAV model. Then,a fixed-time integral sliding mode control(FXISMC) is combined with the FXDO to achieve strong robustness and chattering reduction. Bi-limit homogeneity theory and Lyapunov theory are applied to provide detailed proof of the fixed-time stability. Finally, numerical simulation experimental results verify the robustness of the proposed algorithm to model parameter uncertainties and wind disturbances. In addition, the proposed algorithm is deployed in a open-source UAV autopilot and its effectiveness is further demonstrated by hardware-in-the-loop experimental results.

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Energy consumption optimization for edge computing-supported cellular networks based on optimal transport theory

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Science China(Information Sciences) 2024年第2期67卷 201-218页

作者： Xiangyu LV Xiaohu ge Yi ZHONG Qiang LI Yong XIAO School of Electronic Information and Communications Huazhong University of Science and Technology

With advancements in mobile communication technologies, there have been multiple user device(UD) connections to cellular networks. Because of changes in the spatial distribution of UDs and application requirements, the traditional offloading mechanism based on the nearest distance will result in heavy loads for some base stations(BSs). Because there is a high-order relationship between the energy consumption of the BS processing tasks and the number of computing tasks, the traditional offloading mechanism will result in high energy consumption, and UD’s offloading decision must be dynamically adjusted. The offloading decision of UDs is optimized based on detailed information about various parameters associated with a network from the standpoint of distribution. This information includes details regarding the spatial distribution of UDs,application requirements, and the offloading period of computing tasks. Based on optimal transport theory,an energy consumption optimization algorithm is suggested to lower the total amount of energy consumed by the offloading process of UDs’ computing tasks by reasonably planning the offloading BSs of the UDs in the networks. The simulation results show that the proposed offloading mechanism based on energy consumption optimization reduces the total energy consumption of the offloading process by 28.09% when compared to the traditional offloading mechanism, and the traffic managed by each BS is balanced.

关键词： optimal transport theory edge computing energy consumption reduction dynamic voltage frequency scaling

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