Table of Content

30 April 2023, Volume 29 Issue 2

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Construction strategies and application prospects for bone/cartilage organoids

BAI Long, SU Jiacan

2023, 29(2):  185.  doi:10.12066/j.issn.1007-2861.2458

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Bone/cartilage injuries are common in orthopedics and are increasing annually. Treating these injuries is a clinical problem and is also a hot spot in regenerative medicine research. Currently, bone tissue engineering is used to construct bioactive scaffold materi-als loaded with seed cells to promote bone/cartilage repair. However, this technology lacks multi-dimensional and multi-level mechanism analysis and orderly regulation of biomateri-als in different stages of the bone/cartilage regeneration process, various cells, and specific microenvironment, and spatial bone/cartilage microenvironment characteristics cannot be effectively induced. The limited osteogenic/chondrogenic activity greatly limits its clinical repair effect. Therefore, there is an urgent need to develop revolutionary research tools and technologies to mimic the structure and physiological functions of bone/cartilage in a low-cost and simple manner, to simulate the occurrence of such diseases under specific conditions, replicate pathological characteristics, and use them for pathogenesis research,to ultimately promote bone/cartilage regeneration and repair. Organoids technology offers a unique solution for regenerative medicine research. Bone/cartilage organoids is a new concept that has emerged in recent years, and domestic research is limited. This article covers the development, construction strategy, evaluation and characterization, mechanism exploration, and clinical application of bone/cartilage organoids, aiming to provide a refer-ence for scholars interested in this field, promote the clinical application of bone/cartilage organoids, improve the repair effect of bone/cartilage injuries, and provide a new interven-tion strategy for clinically promoting the orderly regeneration and repair of bone/cartilage tissue.



Separation and extraction of wear debris of vitamin E-stabilized high cross-linked polyethylene artificial knee joints

ZHENG Ye, HUANG Xiuling, FENG Jing, ZHU Junjun, HUA Zikai

2023, 29(2):  200.  doi:10.12066/j.issn.1007-2861.2475

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Vitamin E stabilized highly cross-linked polyethylene (VE/HXLPE) is a antiox-idant material with low wear, and it is unknown whether the wear debris of this material can be extracted by the existing standard methods. Based on standard, this paper used acid digestion method to degrade the calf serum protein in vitro wear test, and set different sampling volume of the digestive fluid to explore its influence on the characteristics of the wear debris. The results show that changing the sampling volume in the extraction method will affect the quantity, volume and morphology distribution of the extracted debris. The quantity of VE/HXLPE wear debris extracted by the existing standard is small, and it is difficult to achieve the characterized quantity. Increasing the sampling volume of digestive fluid can effectively improve this problem, which is more suitable for extracting low-wear VE/HXLPE wear debris.



Research progress of non-coding RNAs in liver cancer

YANG Qianqian, TIAN Hui, WANG Guangzhi, MA Zhongliang

2023, 29(2):  211.  doi:10.12066/j.issn.1007-2861.2457

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Liver cancer is the leading global lethal malignancy. Hypoxia in the tumor microenvironment is a hallmark of the tumor microenvironment, and hypoxia-inducible factor-1a is the most important transcriptional regulator in response to hypoxia. Non- coding RNA (ncRNA) play a crucial role in regulating the pathogenesis and progression of hepatocellular carcinoma (HCC). This review comprehensively summarizes the pathological roles of ncRNA in hepatocarcinogenesis, epithelial-mesenchymal transition, and angiogen- esis under hypoxic environments, and discusses the potential applications of ncRNA as diagnostic tools and therapeutic targets for human HCC.



Progress in research on the role of the Wnt/b-catenin pathway in immune checkpoint inhibitor resistance

2023, 29(2):  224.  doi:10.12066/j.issn.1007-2861.2476

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The Wnt/b-catenin signaling pathway has been one of the most common molec- ular targets of cancer treatment, owing to its involvement in the formation and development of many malignant tumors. It is also signi¯cantly involved in tumor immunoregulation, and abnormally activated Wnt/b-catenin signaling is closely linked to the immunosuppressive microenvironment of tumors. Immune checkpoint inhibitors have been widely studied and used for cancer treatment, but using inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) results in tumor drug resistance and low patient response rates. Activation of the Wnt/b-catenin pathway inhibits CD8+ T cell in¯ltration into the tumor microenviron- ment, which inhibits anti-tumor immune response and induces immune checkpoint inhibitor resistance. This review focuses on the relationship between the Wnt/b-catenin signaling pathway and immune checkpoints and reviews the research progress on the treatment of malignant tumors utilizing a combination of Wnt/b-catenin and immune checkpoint in- hibitors.



Tissue engineering approach for abdominal wall reconstruction using 3D printed vascular supportive patches made of organ-derived decellularized extracellular matrix

ZHANG Haiguang, WANG Hui, HU Qingxi

2023, 29(2):  234.  doi:10.12066/j.issn.1007-2861.2468

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This study aims to develop 3D printed vascular supportive patches (also called sca®olds) from acellular dermal matrix (ADM) and polylactic acid (PLA) suitable for the reconstruction of abdominal wall defects in an animal model. The design and experimental processing conditions required for 3D printing of implantable patches are optimized. The 3D printed patches were tested for their mechanical strength, surface morphology, cytotox- icity, and biocompatibility. The results were also compared with porcine small intestinal submucosa (PSIS) meshes and PLA meshes as controls. The results indicate that the suture load, tensile strength, hydrophobicity, and degradation rate of the 3D printed patches were signi¯cantly higher than that of PSIS and PLA meshes. In vitro evaluation of cell com- patibility with the 3D printed patches was carried out and indicated that the cells were viable and proliferative during the study period. In vivo evaluation of biocompatibility and abdominal wall reconstructive e±cacy of the 3D printed patches was carried out with rat as the model animal. The results indicate that the defect area was repaired well without any noticeable infection, seroma, hematoma, or other conditions. In conclusion, the present study demonstrated the excellent tissue regenerative performance of the 3D printed ADM- PLA-ADM patches, compared with the PSIS meshes and PLA-only meshes, providing a proof of concept for tension-free closure of the abdominal wall defects using 3D printed patches. Therefore, 3D printed ADM-PLA-ADM patches may be considered for abdomi- nal wall reconstructive applications.



Mechanism of Polygonum cuspidatum in treating diabetic cardiomyopathy based on network pharmacology

CHEN Yiqing, ZHOU Lei

2023, 29(2):  244.  doi:10.12066/j.issn.1007-2861.2459

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To explore the key target and potential mechanism of Polygonum cuspidatum in the treatment of diabetic cardiomyopathy (DCM) by network pharmacology, the main active components of Polygonum cuspidatum were obtained by retrieval of traditional Chi-nese medicine systems pharmacology database and analysis platform (TCMSP) combined with literature review, and the potential targets were predicted. The targets of DCM were obtained by GeneCards and online Mendelian inheritance in man (OMIM) database and the intersection targets were obtained by drawing Venn diagram. The String database and CytoScape software were used to construct the network of Polygonum cuspidatum-active constituents-intersection target and protein-protein interaction (PPI) network. The target gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) en-richment analysis were conducted using the database for annotation, visualization and integrated discovery (DAVID). There were 15 active components and 214 potential targets of Polygonum cuspidatum in treatment of DCM, mainly involving lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, insulin resistance, PI3K-Akt signaling pathway and apoptosis. These results demonstrate that Polygonum cuspidatum plays a key role in the treatment of DCM through multiple active components, multiple targets and multiple pathways.



Mechanism of isobavachalcone in treatment of ulcerative colitis

YANG Ti, LI Shan, DENG Shengqiong

2023, 29(2):  253.  doi:10.12066/j.issn.1007-2861.2470

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The potential mechanism of isobavachalcone in tr ulcerative colitis (UC) treat-ment was explored using network pharmacology, Gene Expression Omnibus (GEO) se-quencing data, and molecular docking. Isobavachalcone targets were obtained from Pub-Chem and other databases. Disease targets of UC were obtained from GeneCards, Dis-GeNET, and the GEO database. The intersection of two data sets was used to obtain isobavachalcone targets for UC. The core targets were screened by constructing the in-tersection gene protein interaction network, and the binding activity between drugs and core targets was preliminarily verified using molecular docking. In total, 107 drug and disease intersection genes were obtained. Enrichment analysis was predominantly related to inflammation. Core targets AKT1, MMP9, EGFR, IGF1, and SRC were obtained by screening. Good binding activity between isobavachalcone and core targets was confirmed by molecular docking simulation. Accordingly, the therapeutic role of isobavachalcone in UC may be mediated via the regulation of inflammation-related signaling pathways by acting on core targets, providing data support for subsequent in-depth studies.



Biological effects of typical antidepressants on SKBR3/MCF-7 human breast cancer cells

Haoran Zhao, Wei Peng, Bingli Lei, Lanbing Xu, Mengjie Xu

2023, 29(2):  264.  doi:10.12066/j.issn.1007-2861.2310

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The selective serotonin reuptake inhibitor fluoxetine, tricyclic antidepressants amitriptyline and doxepin, and selective norepinephrine reuptake inhibitor mianserin are currently commonly used antidepressants. However, the non-target toxicity of these drugs is unclear. The cytotoxicity of fluoxetine, amitriptyline, mianserin, and doxepin were tested using SKBR3 and MCF-7 human breast cancer cell lines. Biological effects end-points included cell proliferation, intracellular reactive oxygen species (ROS), calcium ion (Ca2+) concentration changes, and DNA damage. Exposure to 0.001∼10 µmol fluoxetine for 24 h significantly increased viability of SKBR3 cells. Cell viability was significantly inhibited when the concentrations of fluoxetine, amitriptyline, and mianserin were higher than 10 µmol/L. Exposure to low concentrations of fluoxetine and amitriptyline for 24 h significantly increased intracellular ROS levels, while mianserin and doxepin exposure for 3 h significantly elevated intracellular ROS levels. Concentrations of 0.001∼10 µmol/L of the four antidepressants for 24 h had no significant influence on intracellular Ca2+ concentra-tion change, but concentrations higher than 10 µmol/L significantly increased intracellular Ca2+ levels. The comet assay showed that 0.1 and 1 µmol/L fluoxetine slightly induced DNA damage in SKBR3 cells. Cytotoxicity of fluoxetine and amitriptyline was also exam-ined in MCF-7 cells. The evaluated biological effect endpoints including cell proliferation, and intracellular ROS and Ca2+ concentration changes. Similar to SKBR3 cells, only fluoxetine promoted the proliferation of MCF-7 cells at low concentrations. At higher exposure concentrations, fluoxetine and amitriptyline significantly increased intracellular Ca2+ levels. However, fluoxetine and amitriptyline only significant increased intracellular ROS levels at higher exposure concentrations of 25 and 50 µmol/L, which differed from the observation that they can induce ROS generation in SKBR3 cells at low concentrations. These results provide basic experimental data to evaluate the non-target toxicity of these antidepressants.



First-principles study on interactions between hydrogenated two-dimensional atomic diamonds with hydrogen vacancy and indoxyl sulfate and water molecules

GENG Junjie, ZHANG Zhaochun, YAN Qizhen, GUO Haibo, WANG Yang

2023, 29(2):  277.  doi:10.12066/j.issn.1007-2861.2447

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The aim of this study was to construct hydrogenated two-dimensional cu-bic atomic diamonds with hydrogen vacancy-hydrogenated cubic diamond (Hv-HCD) and without hydrogen vacancy (HCD). Furthermore, the isolated monolayer of hexagonal boron nitride (h-BN) or graphene (G) and Hv-HCD were reassembled into van de Waals het-erostructures, h-BN/Hv-HCD, and G/Hv-HCD. Based on first-principles, the Fukui func-tions of water, indoxyl sulfate, and the constructed hydrogenated two-dimensional cubic atomic diamonds with hydrogen vacancy were calculated. The largest values of f+(r) and f−(r) lie around the carbon atom close to the hydrogen vacancy, implying that the carbon atom was the nucleophilic and electrophilic reactive site. The results indicate that a water molecule forms a hydrogen bond with the carbon atom close to the hydrogen vacancy of the hydrogenated two-dimensional atomic diamonds with hydrogen vacancy. The indoxyl phosphate molecule is degraded into 3-indolone and sulfur dioxide at the carbon atom close to the hydrogen vacancy site. The hydroxyl in the sulfonic group forms an alcoholic hy-droxyl with the carbon atom close to the hydrogen vacancy. The phenomena described here could provide a foundation for investigating the essential materials for the development of bioactive or human blood toxic molecule sensors based on two-dimensional atomic crystals.



Planning method for offshore wind farm integration system considering multi-agent game

LIU Lujie, LI Chuanwen, LIU Zhibin, HUANG Lingling, MA Shiwei

2023, 29(2):  287.  doi:10.12066/j.issn.1007-2861.2448

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Offshore wind power can provide efficient and clean new energy and is an im-portant strategic support for the transformation of China’s energy structure. However, the planning of its access system does not sufficiently account for the effect of the interaction between multiple stakeholders in an uncertain competitive market environment. Hence, an offshore wind farm integration system planning model considering a multi-agent game is proposed herein, where the characteristics of an offshore wind power integration system with various investment subjects and operating modes are combined and the interests of multiple participants are considered. The access of the integration system method and the investment and operation cooperation mode are optimised to obtain an optimal planning scheme of the offshore wind power integration system, thus providing a reference for the scientific and flexible planning and effective operation management of offshore wind farm integration systems under multi-agent investment and operation.



Preparation and electrochemical performances of LiNi0.8Co0.1Mn0.1O2 using an in situ gel system

HU Yao, GONG Jianyang, YOU Wanli, LIU Hongjiang, CHEN Guorong, SHI Liyi,

2023, 29(2):  302.  doi:10.12066/j.issn.1007-2861.2305

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To improve the energy density of lithium-ion batteries, a high-nickel ternary cathode material LiNi0.8Co0.1Mn0.1O2 (NCM811) has attracted extensive attention. The raw materials for preparing NCM811 are uniformly dispersed in a high-temperature starch solution by utilizing the characteristic that starch forms a solution at high temperatures and condenses into a gel at lower temperatures. A gel with homogeneous decentralized metal ions was observed, and the NCM811 was prepared by calcining in an air atmosphere, as opposed to the conventional method that uses an oxygen atmosphere. The effects of starch content on the crystal structure, granule size, and electrochemical performance of electrode materials were examined. For 10% starch concentration, particle size was approx-imately 500 nm, coulombic efficiency was 82.88%, discharge specific capacity at 1.0 C was 146.0 mA·h·g−1, and capacity retention for 100 cycles at 1.0 C was 80.14%. The reduc-tion in particle size of the material was attributed to the space confinement effect of the starch gel and the inhibition of particle aggregation and growth during calcination. The small particle size accelerates the migration between electrode and electrolyte, reducing the transport distance of lithium ions. Because of the existence of amylum, the surface of the material contains residual carbon, which enhances the conductivity of the material, thus improving the electrochemical performance.



Modification of LiNi_0.8Co_0.1Mn_0.1O₂ cathode material with ultra-thin TiO₂ coating by atomic layer deposition

Zhu Mingyuan, LIU Wenbon, LI Ying, LIU Yang, LI Wenxian, ZHANG Jiujun

2023, 29(2):  312.  doi:10.12066/j.issn.1007-2861.2319

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The nickel-rich cathode, LiNixCoyMn1−x−yO2 (NCM, ω(Ni)>60%), suffers from phase transitions on the surface of particles during cycling that cause the electrolyte by-product HF to corrode the material and cause the dissolution of transition metal ions. These problems seriously affect the application of NCMs. In this study, atomic layer deposition (ALD) was used to uniformly deposit a TiO2 coating on the surface of a LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode material to improve its electrochemical performance. The results demonstrated a significant improvement in the performance of NCM811 after ALD of TiO2. The ultra-thin TiO2 coating hindered direct contact between the NCM811 active particles and the electrolyte, which improved the cycle stability of the NCM811. The ultra-thin coating did not affect the transmission of lithium ion during cycling. This method for ALD opens a new avenue for the surface modification of electrode materials.



Vacancy trapping during HCP-Mg solidification under different degrees of undercooling

FU Jiahao, ZHANG Boyang, ZHANG Kai, ZHOU Tao, WANG Hao, WU Yongquan

2023, 29(2):  323.  doi:10.12066/j.issn.1007-2861.2318

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Different molecular dynamics (MD) techniques were used to simulate the solid-ification and annealing processes of hexagonal close-packed (HCP) metal Mg under deep, medium, and shallow undercooling conditions. A newly constructed time-averaged atomic volume spectrum (TAVS) method was then utilized to locate and analyse the trapped va-cancies. The results showed that the vacancy trapping effect worked dramatically during solidification, meaning that the greater the degree of undercooling, the higher was the con-centration of trapped vacancies. In addition, the trapping concentration was much higher than the corresponding equilibrium concentration. Moreover, it was found that HCP-Mg had a certain number of self-interstitial atoms during the solidification process, which con-trasted fully with the more symmetrical face-centred cubic (FCC) metal Al. Finally, the atomic cage of vacancy in HCP-Mg featured a remarkable outward displacement instead of the generally accepted inward displacement of vacancy atoms (VA) in metals.



Preparation and electrochemical properties of polyatomic doped melamine foam-based carbon electrodes

WU Yanling, YAN Hao, DAI Yang, ZHANG Baohua

2023, 29(2):  336.  doi:10.12066/j.issn.1007-2861.2358

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The carbonized melamine foam (MF) was activated by niobium pentachloride (NbCl5) to enrich heteroatoms to obtain polyatomic doped melamine foam-based carbon sponges (NbNOCSs) by heat treatment. NbNOCSs have a good self-supporting three-dimensional network structure. They can be directly used as monolithic electrodes without any additives. The results show that the activation of NbCl5 plays an important role in improving the electrochemical properties of NbNOCSs electrodes. Compared with NbNOCS without NbCl5 activation treatment, NbNOCS-1/3 (NbCl5/MF with a primary carbonization weight ratio of 1∶3) shows better electrochemical performance due to its unique pore structures, rich pseudocapacitive active species, and good ion transfer characteristics. Moreover, it exhibits a high specific capacitance (173.4 F·g −1 at a current density of 0.5 A·g −1 ) and high capacitance retention (59.49% at 50 A·g −1 ), as well as a good electrochemical cyclability (90.78% after 10 000 cycles at 10 A·g −1 ).



Preparation of dumbbell-shaped silica abrasives and their chemical mechanical polishing performances

DONG Yue, LEI Hong, LIU Wenqing

2023, 29(2):  345.  doi:10.12066/j.issn.1007-2861.2329

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In this study, dumbbell-shaped silica abrasives were prepared by an anioninduced assisted growth method and characterized. The effects of the abrasives on the chemical mechanical polishing (CMP) performances of zirconia ceramics were then studied. The results showed that the abrasives had good stability and dispersion and exhibited excellent CMP properties. Compared with spherical silica abrasives, the material removal rate of the dumbbell-shaped silica abrasives increased by 39%, and the surfaces of the zirconia ceramics were flat and smooth following polishing, where the surface roughness was 1.960 nm. This was due to the fact the polishing fluid with the abrasives had good wettability and adequately contacted the surfaces of the zirconia ceramics, which helped to induce solid-phase chemical reactions. In addition, the coefficient of friction of the dumbbell-shaped silica was higher, significantly enhancing the mechanical effect.



Elementary waves of the nonlinear hyperbolic system for blood flow in veins

2023, 29(2):  355.  doi:10.12066/j.issn.1007-2861.2362

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This paper studied the elementary waves for the blood flow in veins. The blood flow in veins could be described by a 3 × 3 nonlinear partial differential equations. It was a non strict hyperbolic system. Using the characteristic analysis method, the elementary waves, including rarefaction wave, shock wave, and stationary wave, were obtained constructively. In particular, for stationary wave in blood flow in veins, it was proved that there existed a region Ω in the phase space where stationary wave could be connected by a state when the given state was outside the region