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Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a

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World Journal of Stem Cells 2024年第2期16卷 191-206页

作者： Fan Yang Wan-Qi Xiong Chen-zhi Li Ming-Jian Wu xiu-zhi zhang Chun-Xiao Ran Zhen-Hao Li Yan Cui Bao-Yi Liu De-Wei Zhao Department of Orthopedics Affiliated Zhongshan Hospital of Dalian UniversityDalian 116001Liaoning ProvinceChina

BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examinat

关键词： Exosomes Osteoarthritis Mesenchymal stem cells MicroRNA-29a Intra-articular injection

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Mathematical model of coupled thermo-mechanical behavior during plane strain compression of 06Cr19Ni9NbN steel

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Journal of Iron and Steel Research(International) 2018年第11期25卷 1179-1188页

作者： Yong-xing Jiao Yue Xu Jian-sheng Liu Jing-dan Li xiu-zhi zhang College of Materials Science and Engineering Taiyuan University of Science and Technology Taiyuan 030024ShanxiChina

The process of plane strain compression of 06Cr19Ni9NbN steel was carried out in the temperature range of 1000-1200℃ and the reduction ratio range of 10-50%.Combining the finite element numerical simulation,a new constitutive model of thermal deformation was established, which provides the theoretical basis to optimize the plarie strain compression process of the steel.The temperature and grain size at different regions were achieved by experiment and simulation,respectively.According to the results,the mathematical models of stress and temperature during the plane strain compression were established by mathematical analysis method.The new temperature models were established in three regions,respectively,and the stress models took account of the variation of temperature and'st^rain rate.Finally,by comparing the results of calculation,numerical simulation and experiment,the accuracy and validity of these mathematical models were verified.

关键词： Plane strain compression Coupled thermo-mechanical behavior 06Cr19Ni9NbN steel Numerical simulation Mathematical model

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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi zhang zhi-Ying Wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

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Sequential Fluorescent Labeling Observation of Maxillary Sinus Augmentation by a Tissue-engineered Bone Complex in Canine Model

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International Journal of Oral Science 2009年第1期1卷 39-46页

作者： Xin-quan Jiang Shao-yi Wang Jun Zhao xiu-li zhang zhi-yuan zhang Shanghai Research Institute of Stomatology Shanghai Key Laboratory of Stomatolgoy Shanghai Ninth People＇s Hospitalaffiliated to Shanghai Jiao Tong University School of Medicine Shanghai China

Aim To evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex of β-tricalcium phosphate （β-TCP） and autologous osteoblasts in dogs. Methodology Autologous osteoblasts from adult Beagle dogs were cultured in vitro. They were further combined with β-TCP to construct the tissue-engineered bone complex. 12 cases of maxillary sinus floor elevation surgery were made bilaterally in 6 animals and randomly repaired with the following 3 groups of materials： Group A （osteoblasts/D-TCP）; Group B （β-TCP）; Group C （autogenous bone）（n=4 per group）. A polychrome sequential fluorescent labeling was performed post-operatively and the animals were sacrificed 24 weeks after operation for histological observation.Results Our results showed that autologous osteoblasts were successfully expanded and the osteoblastic phenol- types were confirmed by ALP and Alizarin red staining. The cells could attach and proliferate well on the surface of the ~3-TCP scaffold. The fluorescent and histological observation showed that the tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than β-TCP along or even autologous bone. It had also maximally maintained the elevated sinus height than both control groups. Conclusion Porous 13-TCP has served as a good scaffold for autologous osteoblasts seeding. The tissue-engineered bone complex with β-TCP and autologous osteoblasts might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation.

关键词： maxillary sinus augmentation tissue engi-neering β-tricalcium phosphate osteoblasts fluorescentlabeling

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A bifunctional POM-based Cu-viologen complex with mixed octamolybdate clusters for rapid oxidation desulfurization and effective photogeneration of hydrogen

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Rare Metals 2024年第1期43卷 236-246页

作者： Lin Yang Zhong zhang Chao-Nan zhang xiu-Li Wang College of Chemistry and Materials Engineering Bohai UniversityJinzhou 121013China Professional Technology Innovation Center of Liaoning Province for Conversion Materials of Solar Cell Bohai UniversityJinzhou 121013China

The design and synthesis of catalysts for the oxidation desulfurization and production of hydrogen are extremely important for solving environmental pollution and energy shortage.Herein,a novel bifunctional [α-Mo_(8)O_(26)]^(4-)/[β-Mo_(8)O_(26)]^(4-)-based Cu-viologen complex H_(4)[Cu_(2)~ⅠCl_(2)(Hbcbpy)_(4)] [α-Mo_(8)O_(26)] [β-Mo8O_(26)]·H_(2)O(BHU-2,Hbcbpy=1-(4-carboxybenzyl)-4,4'-bipyridinium) was synthesized and characterized by single-crystal X-ray diffraction(XRD),infrared radiation spectra,powder X-ray diffraction(PXRD) and X-ray photoelectron spectroscopy(XPS) spectra.The structural characteristic of BHU-2 is the presence of two types of octamolybdate clusters [α-Mo_(8)O_(26)]^(4-)/[β-Mo_(8)O_(26)]^(4-)and a new binuclear Cu~Ⅰ-Hbcbpy complex linked by Cl-bridges[Cu_(2)ⅠCl_(2)(Hbcbpy)_(4)]^(4+).BHU-2 as a heterogeneous catalyst exhibits excellent activities to the oxidation desulfurization and photocatalytic hydrogen production.At room temperature,BHU-2 can catalyze 96% conversion of methyl phenyl sulfide with 98% selectivity,and the process obeys the pseudo-first-order reaction kinetic with the half-life of9.6 min.The notorious 2-chloroethyl ethyl sulfide can achieve 99% conversion with 98% selectivity within only1 min at the presence of BHU-2,and the turnover frequency(TOF) is up to 7400 h^(-1).BHU-2 also exhibits high catalytic activity for the oxidation of other aromatic and aliphatic thioethers within short time at room temperature.Furthermore,BHU-2 shows a high catalytic activity for visible-light-driven hydrogen evolution with an H_(2) evolution rate of 1677.85 μmol·g^(-1)·h^(-1) within 10 h.Moreover,the catalytic activities do not decrease evidently after three cycles,revealing the prominent structural stability and recyclability.

关键词： Polyoxometalate Metal-organic complex Viologen Oxidation desulfurization Photocatalytic hydrogen production

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Deciphering and integrating invariants for neural operator learning with various physical mechanisms

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National Science Review 2024年第4期11卷 111-122页

作者： Rui zhang Qi Meng zhi-Ming Ma Academy of Mathematics and Systems Science Chinese Academy of Sciences(CAS) Microsoft Research

Neural operators have been explored as surrogate models for simulating physical systems to overcome the limitations of traditional partial differential equation(PDE) solvers. However, most existing operator learning methods assume that the data originate from a single physical mechanism, limiting their applicability and performance in more realistic scenarios. To this end, we propose the physical invariant attention neural operator(PIANO) to decipher and integrate the physical invariants for operator learning from the PDE series with various physical mechanisms. PIANO employs self-supervised learning to extract physical knowledge and attention mechanisms to integrate them into dynamic convolutional layers.Compared to existing techniques, PIANO can reduce the relative error by 13.6%–82.2% on PDE forecasting tasks across varying coefficients, forces or boundary conditions. Additionally, varied downstream tasks reveal that the PI embeddings deciphered by PIANO align well with the underlying invariants in the PDE systems, verifying the physical significance of PIANO.

关键词： neural operator PDE solver contrastive learning physical invariants

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P-symmetric Subharmonic Solutions for Nonlinear Hamiltonian Systems

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Acta Mathematica Sinica,English Series 2024年第6期40卷 1388-1408页

作者： Duan zhi zhang zhi Hao ZHAO School of Mathematical Sciences Nankai UniversityTianjin 300071P.R.China

In this paper,we prove that for each positive k≡1 mod m there exists a P-symmetric kmτ-periodic solution xk for asymptotically linear mτ-periodic Hamiltonian systems,which are nonautonomous and endowed with a P-symmetry.If the P-symmetric Hamiltonian function is semi-positive,one can prove,under a new iteration inequality of the Maslov-type P-index,that xk_(1) and xk_(2) are geometrically distinct for k_(1)/k_(2)≥(2n+1)m+1;and xk_(1),xk_(2) are geometrically distinct for k_(1)/k_(2)≥m+1 provided xk_(1) is non-degenerate.

关键词： P-symmetric subharmonic Hamiltonian systems Maslov-type index theory iteration inequality asymptotically linear

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Enhanced memristor performance via coupling effect of oxygen vacancy and ferroelectric polarization

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Journal of Materials Science & Technology 2024年第4期171卷 139-146页

作者： zhi Yun Yue zhi Dong zhang Zhan Jie Wang Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

As a new type of nonvolatile memory,the resistive memristor has broad application prospects in in-formation storage and neural computing based on its excellent resistive switching(RS)performance.At present,it is still a great challenge to improve both ferroelectric polarization and leakage current to achieve a high RS on/offratio of ferroelectric memristors.Herein,epitaxial Pb(Zr_(0.40)Ti_(0.60))O_(3)(PZT)thin films with low content Ca doping were deposited on the Nb:SrTiO_(3)substrate to prepare PCZT/NSTO het-erostructures and their RS behaviors were studied.The research findings show that compared with pure PZT film,the ferroelectric polarization of 1-mol%-Ca-doped PZT film is slightly improved,while the leak-age current is increased by three orders of magnitude.Therefore,the RS on/offratio reaches 2.5×10^(5),about three orders of magnitude higher than pure PZT films.The theoretical analysis reveals that the RS behavior of PCZT/NSTO heterostructures is controlled by the PCZT/NSTO interfacial barrier and the space charge-limited current mechanism.Our results demonstrate that the ferroelectricity and electricity of ferroelectric thin films can be improved simultaneously by doping low-content Ca ions to increase the RS performance,which provides a good reference for the development of high-performance ferroelectric memristor devices.

关键词： Ferroelectric memristor Ca-doped PZT Ferroelectric polarization Oxygen vacancies Resistive switching

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Macrophage Inhibitory Cytokine-1 as a Novel Diagnostic and Prognostic Biomarker in Stage I and II Nonsmall Cell Lung Cancer

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Chinese Medical Journal 2016年第17期129卷 2026-2032页

作者： Yu-Ning Liu Xiao-Bing Wang Teng Wang Chao zhang Kun-Peng zhang xiu-Yi zhi Wei zhang Ke-Lin Sun Department of Thoracic Surgery Detection Center of Tumor Biology Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China

Background： Increased level of serum macrophage inhibitory cytokine- 1 （MIC- 1 ）, a member oftransfonning growth thctor-β superfamily, was found in patients with epithelial tumors. This study aimed to evaluate whether serum level of MIC-I can be a candidate diagnostic and prognostic indicator for early-stage nonsmall cell lung cancer （NSCLC）. Methods： A prospective study enrolled 152 patients with Stage I-II NSCLC, who were followed up after surgical resection. Forty-eight patients with benign pulmonary disease （BPD） and 105 healthy controls were also included in the study. Serum M IC- 1 levels were measured using an enzyme-linked immunosorbent assay, and the association with clinical and prognostic features was analyzed. Results： In patients with NSCLC, serum protein levels of M IC-I were significantly increased compared with healthy controls and BPD patients （all P 〈 0.001 ）. A threshold of 1000 pg/ml ofM IC-1 was found in patients with early-stage （Stage 1 and II） NSCLC, with sensitivity and specificity of 70.4% and 99.0%, respectively. The serum levels ofMIC- ] were associated with age （P = 0.001 ）, gender （P = 0.030）, and T stage （P = 0.022）. Serum MIC-1 threshold of 1465 pg/ml was found in patients with poor early outcome, with sensitivity and specificity of 72.2% and 66.1%, respectively. The overall 3-year survival rate of NSCLC patients with high serum levels of MIC-1 （〉I 465 pg/ml） was lower than that of NSCLC patients with low serum MIC-1 levels （77.6% vs. 94.8%）. Multivariate Cox regression survival analysis showed that a high serum level ofMIC- 1 was an independent risk factor lbr reduced overall survival （hazard ratio - 3.37, 95% confidential interval： 1.09-10.42, P = 0.035）. Conclusion： The present study suggested that serum M1C-I may be a potential diagnostic and prognostic biomarker ~cbr patients with early-stage NSCLC.

关键词： Macrophage Inhibitory Cytokine-1 Nonsmall Cell Lung Cancer Sensitivity Specificity

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Advances in MET tyrosine kinase inhibitors in gastric cancer

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Cancer Biology & Medicine 2024年第6期21卷 484-498页

作者： Yifan zhang Lin Shen zhi Peng Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Oncology Peking University Cancer Hospital & Institute State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Department of Gastrointestinal Oncology Peking University Cancer Hospital & Institute

Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally. Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics, the management of gastric cancer calls for better-defined, biomarker-guided, molecular-based treatment strategies. MET is a receptor tyrosine kinase mediating important physiologic processes, such as embryogenesis, tissue regeneration, and wound healing. However, mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types, including gastric cancer, and is associated with poor patient outcomes. As such, MET-targeting therapies are being actively developed and promising progress has been demonstrated, especially with MET tyrosine kinase inhibitors. This review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib, tepotinib, capmatinib, and crizotinib. Building on current knowledge, this review further discusses existing challenges in MET alterations testing, possible resistance mechanisms to MET inhibitors, and future directions of MET-targeting therapies.

关键词： Gastric cancer MET alterations MET testing MET tyrosine kinase inhibitors savolitinib

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