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IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： WEN ge YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI zhao Department of Immunology Nanjing Medical UniversityNanjing210000China Key Laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu Key Laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-jin Ai Ling-Juan Chen Li-Xuan Guo Ya-Ping Wang Zi-Yi zhao Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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High-efficiency sodium storage of Co_(0.85)Se/WSe_(2) encapsulated in N-doped carbon polyhedron via vacancy and heterojunction engineering

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Carbon Energy 2024年第1期6卷 94-107页

作者： Ya Ru Pei Hong Yu Zhou Ming zhao Jian Chen Li Xin ge Wei Zhang Chun Cheng Yang Qing Jiang Key Laboratory of Automobile Materials(Jilin University) Ministry of EducationSchool of Materials Science and EngineeringJilin UniversityChangchunChina Jilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy Materials Electron Microscopy CenterJilin UniversityChangchunChina

With the advantage of fast charge transfer,heterojunction engineering is identified as a viable method to reinforce the anodes'sodium storage performance.Also,vacancies can effectively strengthen the Na+adsorption ability and provide extra active sites for Na+adsorption.However,their synchronous engineering is rarely reported.Herein,a hybrid of Co_(0.85)Se/WSe_(2) heterostructure with Se vacancies and N-doped carbon polyhedron(CoWSe/NCP)has been fabricated for the first time via a hydrothermal and subsequent selenization strategy.Spherical aberration-corrected transmission electron microscopy confirms the phase interface of the Co_(0.85)Se/WSe_(2) heterostructure and the existence of Se vacancies.Density functional theory simulations reveal the accelerated charge transfer and enhanced Na+adsorption ability,which are contributed by the Co_(0.85)Se/WSe_(2) heterostructure and Se vacancies,respectively.As expected,the CoWSe/NCP anode in sodium-ion battery achieves outstanding rate capability(339.6 mAh g^(−1) at 20 A g^(−1)),outperforming almost all Co/W-based selenides.

关键词： Co_(0.85)Se/WSe_(2)heterostructure density functional theory simulations N-doped carbon polyhedron Se vacancies sodium-ion batteries

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Ethanol extract of Abelmoschus manihot suppresses endoplasmic reticulum stress in contrast-induced nephropathy

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 17-27,I0002,I0003页

作者： Xin Lin Xin Lu Yun-He zhao Yi-Bei Wang Ru-ge Niu Xiao-Hu Chen Department of Cardiology Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjingJiangsu 210004China

Objective:To explore the efficacy and potential mechanisms of the ethanol extract of Abelmoschus manihot(L.)Medic in contrast-induced nephropathy(CIN).Methods:CIN rat models and human renal proximal tubular cells(HK-2)with iopromide-induced injury were employed to mimic CIN conditions.The effect of Abelmoschus manihot extract on the rat models and HK-2 cells was evaluated.In rat models,kidney function,histology,oxidative stress and apoptosis were determined.In HK-2 cells,cell viability,apoptosis,mitochondrial membrane potential,and endoplasmic reticulum stress were assessed.Results:Abelmoschus manihot extract significantly improved structural and functional impairments in the kidneys of CIN rats.Additionally,the extract effectively mitigated the decline in cellular viability and reduced iopromide-induced oxidative stress and lipid peroxidation.Mechanistic investigations revealed that Abelmoschus manihot extract prominently attenuated acute endoplasmic reticulum stress-mediated apoptosis by downregulating GRP78 and CHOP protein levels.Conclusions:Abelmoschus manihot extract can be used as a promising therapeutic and preventive agent in the treatment of CIN.

关键词： Contrast-induced nephropathy Abelmoschus manihot extract ER stress Apoptosis GRP78 CHOP

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A real-time intelligent lithology identification method based on a dynamic felling strategy weighted random forest algorithm

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Petroleum Science 2024年第2期21卷 1135-1148页

作者： Tie Yan Rui Xu Shi-Hui Sun zhao-Kai Hou jin-Yu Feng School of Petroleum Engineering Northeast Petroleum UniversityDaqing163318HeilongjiangChina Sanya Offshore Oil&Gas Research Institute Northeast Petroleum UniversitySanya572025HainanChina

Real-time intelligent lithology identification while drilling is vital to realizing downhole closed-loop drilling. The complex and changeable geological environment in the drilling makes lithology identification face many challenges. This paper studies the problems of difficult feature information extraction,low precision of thin-layer identification and limited applicability of the model in intelligent lithologic identification. The author tries to improve the comprehensive performance of the lithology identification model from three aspects: data feature extraction, class balance, and model design. A new real-time intelligent lithology identification model of dynamic felling strategy weighted random forest algorithm(DFW-RF) is proposed. According to the feature selection results, gamma ray and 2 MHz phase resistivity are the logging while drilling(LWD) parameters that significantly influence lithology identification. The comprehensive performance of the DFW-RF lithology identification model has been verified in the application of 3 wells in different areas. By comparing the prediction results of five typical lithology identification algorithms, the DFW-RF model has a higher lithology identification accuracy rate and F1 score. This model improves the identification accuracy of thin-layer lithology and is effective and feasible in different geological environments. The DFW-RF model plays a truly efficient role in the realtime intelligent identification of lithologic information in closed-loop drilling and has greater applicability, which is worthy of being widely used in logging interpretation.

关键词： Intelligent drilling Closed-loop drilling Lithology identification Random forest algorithm Feature extraction

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Improving actionable warning identification via the refined warning-inducing context representation

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Science China(Information Sciences) 2024年第5期67卷 321-322页

作者： Xiuting ge Chunrong FANG Xuanye LI Quanjun ZHANG Jia LIU Zhihong zhao Zhenyu CHEN State Key Laboratory for Novel Software Technology Nanjing University

Static analysis tools(SATs) have shown potential ability in software quality assurance [1]. However, SATs report an overwhelming number of warnings, where most warnings are unactionable ones(i.e., warnings that are not acted on or fixed by developers). It is not a trivial task for developers to find actionable warnings(i.e., warnings that are acted on and fixed by developers) in all reported warnings. Hence,the excessive unactionable warnings seriously impede the usability of SATs [2].

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Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn

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Current Medical Science 2024年第2期44卷 369-379页

作者： Ji LUO jin ZHOU jing-zeng LUO Hai-long WANG Xue-ling zhao Ru-dan ZHOU Department of Intensive Care Unit The First People's Hospital of ZiyangZiyang 641300China Department of Orthopedics Kunming Medical University Second Affiliated HospitalKunming 650033China Department of Orthopedics Kunming Medical University First Affiliated HospitalKunming 650032China Department of Orthopedics The Third People's Hospital of Yunnan ProvinceKunming 650200China

Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been determined.The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT.Methods:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT.After screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were evaluated.The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro.Results:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor VIII von Willebrand factor(F8VWF)were selected for analysis in mice.When MMP13 was inhibited,the expression level of PDPN decreased significantly in vitro.In HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation.Conclusions:Inhibiting the expression of MMP13 could reduce the burden of DVT in mice.The mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.

关键词： deep vein thrombosis matrix metalloproteinase 13 podoplanin

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Magnetic resonance imaging techniques for lithium-ion batteries:Principles and applications

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Magnetic Resonance Letters 2024年第2期4卷 22-39页

作者： Hongxin Lin Yanting jin Mingming Tao Yingao Zhou Peizhao Shan Danhui zhao Yong Yang State Key Laboratory for Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials and Department of ChemistryCollege of Chemistry and Chemical EngineeringTan Kah Kee Innovation Laboratory(IKKEM)Xiamen UniversityXiamen361005China School of Energy Xiamen UniversityXiamen361005China

Operando monitoring of internal and local electrochemical processes within lithium-ion batteries(LIBs)is crucial,necessitating a range of non-invasive,real-time imaging characterization techniques including nuclear magnetic resonance(NMR)techniques.This review provides a comprehensive overview of the recent applications and advancements of non-invasive magnetic resonance imaging(MRI)techniques in LIBs.It initially introduces the principles and hardware of MRI,followed by a detailed summary and comparison of MRI techniques used for characterizing liquid/solid electrolytes,electrodes and commercial batteries.This encompasses the determination of electrolytes'transport properties,acquisition of ion distribution profile,and diagnosis of battery defects.By focusing on experimental parameters and optimization strategies,our goal is to explore MRI methods suitable to a variety of research subjects,aiming to enhance imaging quality across diverse scenarios and offer critical physical/chemical insights into the ongoing operation processes of LIBs.

关键词： Lithium-ion batteries Magnetic resonance imaging(MRI) Electrolytes Electrodes Commercial batteries

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Suppression of low-frequency ultrasound broadband vibration using star-shaped single-phase metamaterials

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Defence Technology（防务技术） 2024年第4期34卷 217-224页

作者： Rui zhao Jian Zheng jin Guo Yunbo Shi Hengzhen Feng Jun Tang Jun Liu Science and Technology on Electronic Test&Measurement Laboratory North University of ChinaTaiyuan 030051ShanxiChina School of Mechatronical Engineering Beijing Institute of TechnologyBeijing 100081China

In order to suppress the low-frequency ultrasound vibration in the broadband range of 20 k Hz—100 k Hz,this paper proposes and discusses an acoustic metamaterial with low-frequency ultrasound vibration attenuation properties,which is configured by hybrid arc and sharp-angle convergent star-shaped lattices.The effect of the dispersion relation and the bandgap characteristic for the scatterers in star-shaped are simulated and analyzed.The target bandgap width is extended by optimizing the geometry parameters of arc and sharp-angle convergent lattices.The proposed metamaterial configured by optimized hybrid lattices exhibits remarkable broad bandgap characteristics by bandgap complementarity,and the simulation results verify a 99%vibration attenuation amplitude can be obtained in the frequency of20 k Hz—100 k Hz.After the fabrication of the proposed hybrid configurational star-shaped metamaterial by 3D printing technique,the transmission loss experiments are performed,and the experimental results indicate that the fabricated metamaterial has the characteristics of broadband vibration attenuation and an amplitude greater than 85%attenuation for the target frequency.These results demonstrate that the hybrid configurational star-shaped metamaterials can effectively widen the bandgap and realize high efficiency attenuation,which has capability for the vibration attenuation in the application of highprecise equipment.

关键词： Star-shaped metamaterials Broadband Vibration attenuation Low-frequency ultrasound vibration Transmission loss

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Using Machine Learning to Identify and Optimize Sensitive Parameters in Urban Flood Model Considering Subsurface Characteristics

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International Journal of Disaster Risk Science 2024年第1期15卷 116-133页

作者： Hengxu jin Yu zhao Pengcheng Lu Shuliang Zhang Yiwen Chen Shanghua Zheng Zhizhou Zhu Key Laboratory of Vge of Ministry of Education Nanjing Normal UniversityNanjing 210023China Jiangsu Center for Collaborative Innovation in geographical Information Resource Development and Application Nanjing 210023China

This study presents a novel method for optimizing parameters in urban flood models,aiming to address the tedious and complex issues associated with parameter optimization.First,a coupled one-dimensional pipe network runoff model and a two-dimensional surface runoff model were integrated to construct an interpretable urban flood model.Next,a principle for dividing urban hydrological response units was introduced,incorporating surface attribute features.The K-means algorithm was used to explore the clustering patterns of the uncertain parameters in the model,and an artificial neural network(ANN)was employed to identify the sensitive parameters.Finally,a genetic algorithm(GA) was used to calibrate the parameter thresholds of the sub-catchment units in different urban land-use zones within the flood model.The results demonstrate that the parameter optimization method based on K-means-ANN-GA achieved an average Nash-Sutcliffe efficiency coefficient(NSE) of 0.81.Compared to the ANN-GA and K-means-deep neural networks(DNN) methods,the proposed method better characterizes the runoff generation and flow processes.This study demonstrates the significant potential of combining machine learning techniques with physical knowledge in parameter optimization research for flood models.

关键词： Artifcial neural network Coupled urban fooding model genetic algorithm K-means algorithm Subcatchment delineation Uncertain parameters

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