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Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer

Chinese Medical Journal 2024年第3期137卷 338-349页

作者： feng xu Kun xu Lingling Fan Xintong Li Yiqiu Liu Fang Yang Chengjun Zhu Xiaoxiang guan Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjingJiangsu 210009China The Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment options.The androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)TNBC.However,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits.This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC tissues.Then,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in TNBC.Chromatin immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of AR.Results:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR positive.We further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative TNBC.Mechanistically,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression.Conclusions:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation.Therefore,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

关键词： Androgen receptor Estrogen receptor beta Triple-negative breast cancer NECTIN4 Oncogenic effects Tumor progression

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Emulsifying property,antioxidant activity,and bitterness of soybean protein isolate hydrolysate obtained by Corolase PP under high hydrostatic pressure

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Food Science and Human Wellness 2024年第3期13卷 1271-1278页

作者： Haining guan Chunmei feng Min Ren Xiaojun xu Dengyong Liu Xiaoqin Diao College of Food Science and Technology Bohai UniversityJinzhou 121013China

Enzymatic hydrolysis of proteins can enhance their emulsifying properties and antioxidant activities.However,the problem related to the hydrolysis of proteins was the generation of the bitter taste.Recently,high hydrostatic pressure(HHP)treatment has attracted much interest and has been used in several studies on protein modification.Hence,the study aimed to investigate the effects of enzymatic hydrolysis by Corolase PP under different pressure treatments(0.1,100,200,and 300 MPa for 1-5 h at 50℃)on the emulsifying property,antioxidant activity,and bitterness of soybean protein isolate hydrolysate(SPIH).As observed,the hydrolysate obtained at 200 MPa for 4 h had the highest emulsifying activity index(47.49 m^(2)/g)and emulsifying stability index(92.98%),and it had higher antioxidant activities(44.77%DPPH free radical scavenging activity,31.12%superoxide anion radical scavenging activity,and 61.50%copper ion chelating activity).At the same time,the enhancement of emulsion stability was related to the increase of zeta potential and the decrease of mean particle size.In addition,the hydrolysate obtained at 200 MPa for 4 h had a lower bitterness value and showed better palatability.This study has a broad application prospect in developing food ingredients and healthy foods.

关键词： Soybean protein isolate High hydrostatic pressure Emulsification Antioxidant Bitter taste

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Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

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Science China(Life Sciences) 2024年第4期67卷 698-710页

作者： Runtian Wang Gaigai Li Fangyan Gao feng xu Xintong Li Jian Zhang Jinbo Li Xiaoxiang guan Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China State Key Laboratory of Analytical Chemistry for Life Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China Department of Medical Oncology Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.

关键词： triple-negative breast cancer c-Myc spherical nucleic acid self-assembly

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Enhanced photocatalytic ammonia oxidation activity and nitrogen selectivity over Ag/AgCl/N-TiO_(2) photocatalyst

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Journal of Environmental Sciences 2024年第4期138卷 395-405页

作者： Jiaojiao guan Daorong Li Jiahui feng Peng xu Zhaonian Li Siqi Ge Hongxia Chen Kunfeng Zhang College of Environmental Engineering Henan University of TechnologyZhengzhou 450001China CAS Key Laboratory of Standardization and Measurement for Nanotechnology National Center for Nanoscience and TechnologyBeijing 100190China Department of Chemistry Tsinghua UniversityBeijing 100084China

The removal of ammonia(NH_(3))emitted from agricultural and industrial activities is of great significance to protect human health and ecological environment.Photocatalytic NH_(3)oxidation to N2under mild conditions is a promising strategy.However,developing visible light photocatalysts for NH_(3)oxidation is still in its infancy.Here,we fabricate N-TiO_(2)and Ag/AgCl/N-TiO_(2)photocatalysts by sol-gel and photodeposition methods,respectively.The introduction of N not only endows TiO_(2)with visible light response(absorption edge at460 nm)but also results in the formation of heterophase junction(anatase and rutile).Thus,N-TiO_(2)shows 2.0 and 1.8 times higher than those over anatase TiO_(2)and commercial TiO_(2)for NH_(3)oxidation under full spectrum irradiation.Meanwhile,surface modification of Ag can simultaneously enhance visible light absorption(generating localized surface plasmon resonance effect)and charge separation efficiency.Therefore,the photocatalytic activity of Ag/AgCl/N-TiO_(2)is further improved.Furthermore,the presence of N and Ag also enhances the selectivity of N2product owing to the change of reaction pathway.This work simultaneously regulates photocatalytic conversion efficiency and product selectivity,providing some guidance for developing highly efficient photocatalysts for NH_(3)elimination.

关键词： TiO_(2) Doping Surface modification Photocatalysis NH_(3)elimination

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Nanoforming of transferred metal contacts for enhanced twodimensional field effect transistors

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Nano Research 2024年第4期17卷 3210-3216页

作者： Shuoheng xu Zheng Huang Jie guan Yaowu Hu The Institute of Technological Sciences Wuhan UniversityWuhan 430072China School of Power and Mechanical Engineering Wuhan UniversityWuhan 430072China School of Physics Southeast UniversityNanjing 211189China

Two-dimensional transition metal chalcogenides(2D-TMDs)have attracted much attention because of their unique layered structure and physical properties for transistor applications.Mechanically transferred metal contacts on these low-dimensional materials or their homogeneous and heterogeneous multilayers have generated huge interest to avoid deposition damages.In this paper,we show that there are large physical gaps at both the edge contact and surface contact between the transferred electrodes and the 2D materials.A method called laser shock induced superplastic deformation(LSISD)is proposed to tackle this issue and enhance the performance of the transistors.The enhancement mechanism was investigated by molecular dynamics(MD)simulations of the nanoforming process,atomic force microscopy(AFM),scanning electron microscopy(SEM),transmission electron microscopy(TEM)characterizations of the interfaces,and density functional theory(DFT)modeling.The force effect of laser shock can reduce the contact gap between metals and semiconductors.The electrical performances of the transistors before and after LSISD,along with MD simulations,are used to find the optimal process parameters.In addition,this paper applies the LSISD method to the short-channel MoS_(2)/graphene vertical transistors to show potential improvement in interface contact and electrical properties.This paper demonstrates the first report on using mechanical force induced by laser shock to enhance metal–semiconductor interfaces and transistor performances.

关键词： laser shock nanoforming metal-semiconductor contact electronics two-dimensional transistors

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Beam based alignment using a neural network

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Nuclear Science and Techniques 2024年第4期35卷 108-118页

作者： guan-Liang Wang Ke-Min Chen Si-Wei Wang Zhe Wang Tao He Masahito Hosaka guang-Yao feng Wei xu National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China Diamond Light Source Oxfordshire OX110DEUK

Beams typically do not travel through the magnet centers because of errors in storage rings.The beam deviating from the quadrupole centers is affected by additional dipole fields due to magnetic field feed-down.Beam-based alignment(BBA)is often performed to determine a golden orbit where the beam circulates around the quadrupole center axes.For storage rings with many quadrupoles,the conventional BBA procedure is time-consuming,particularly in the commissioning phase,because of the necessary iterative process.In addition,the conventional BBA method can be affected by strong coupling and the nonlinearity of the storage ring optics.In this study,a novel method based on a neural network was proposed to determine the golden orbit in a much shorter time with reasonable accuracy.This golden orbit can be used directly for operation or adopted as a starting point for conventional BBA.The method was demonstrated in the HLS-II storage ring for the first time through simulations and online experiments.The results of the experiments showed that the golden orbit obtained using this new method was consistent with that obtained using the conventional BBA.The development of this new method and the corresponding experiments are reported in this paper.

关键词： Golden orbit Beam-based alignment Neural network Storage ring

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Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China

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World Journal of Psychiatry 2024年第4期14卷 523-532页

作者： Jing-Wen xu Xiao-Bo guan xue-Ying Wang Yang feng Qi Zhang Jun-Juan Zhu Jian-Hua Chen Department of Medicine Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China The Fourth Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Psychotic DisordersShanghai 200030China The First Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China

BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

关键词： Antipsychotics Risperidone 9-hydroxyrisperidone Plasma drug concentration monitoring Chronic schizophrenia

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Development characteristics and controlling factors of fractures in lacustrine shale and their geological significance for evaluating shale oil sweet spots in the third member of the Shahejie Formation in the Qikou Sag, Bohai Bay Basin

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Petroleum Science 2024年第2期21卷 791-805页

作者： xu Zeng Tao Yang Jian-Wei feng Cong-Sheng Bian Ming guan Wei Liu Bing-Cheng Guo Jin Dong Research Institute of Petroleum Exploration and Development China National Petroleum CorporationBeijing100083China College of Geosciences China University of Petroleum(Beijing)Beijing102249China Key Laboratory of Petroleum Resources and Prospecting China University of Petroleum(Beijing)Beijing102249China School of Earth Sciences China University of PetroleumQingdao266400ShandongChina

Natural fractures are critical for shale oil and gas enrichment and development. Due to the extremely high heterogeneity of shale, the factors controlling the formation of internal fractures, especially horizontal fractures, remain controversial. In this study, we integrate thin section analysis and microcomputed tomography(CT) data from several lacustrine shale samples from the third member(Es3) of the Shahejie Formation, Qikou Sag, Bohai Bay Basin, to assess the fractures in detail. The goal is to reveal the development characteristics, controlling factors, and geological significance for evaluating sweet spots in a shale oil play. The fractures in the Es3contain high-angle structural and horizontal bed-parallel fractures that are mostly shear and extensional. Various factors influence fracture development,including lithofacies, mineral composition, organic matter content, and the number of laminae. Structural fractures occur predominantly in siltstone, whereas bed-parallel fractures are abundant in laminated shale and layered mudstone. A higher quartz content results in higher shale brittleness, causing fractures, whereas the transformation between clay minerals contributes to the development of bedparallel fractures. Excess pore pressure due to hydrocarbon generation and expulsion during thermal advance can cause the formation of bed-parallel fractures. The density of the bed-parallel and structural fractures increases with the lamina density, and the bed-parallel fractures are more sensitive to the number of laminae. The fractures are critical storage spaces and flow conduits and are indicative of sweet spots. The laminated shale in the Es3with a high organic matter content contains natural fractures and is an organic-rich, liquid-rich, self-sourced shale play. Conversely, the siltstone, massive mudstone, and argillaceous carbonate lithofacies contain lower amounts of organic matter and do not have bed-parallel fractures. However, good reservoirs can form in these areas when structural fractures are present

关键词： Fractures Development characteristics Controlling factors Shale oil Sweet spot

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High-current pulsed electron beam modification on microstructure and performance of Cu/CuW diffusion bonding joints

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Rare Metals 2024年第6期43卷 2819-2831页

作者： Na-Na Tian Cong-Lin Zhang Peng Lyu Jin-Tong guan Jie Cai Qing-feng guan Shun Guo School of Materials Science and Engineering Jiangsu University School of Material Science and Engineering Yancheng Institute of Technology Engineering Institute of Advanced Manufacturing and Modern Equipment Technology Jiangsu University

This study investigates the influence of high-current pulsed electron beam（HCPEB） modification on the microstructure and shear strength of Cu/CuW joints.Reliable solid-state diffusion bonding of modified-Cu（MCu） and modified-CuW（M-CuW） was achieved by HCPEB modification pretreatment at a temperature of 800-900 ℃ and a pressure of 5 MPa for 10-50 min.Experiments demonstrate that HCPEB modification facilitates the dissolution of W and Cu,resulting in the formation of a Cu0.4W0.6solid solution and thus enhancing the uniform distribution of microstructures.Additionally,HCPEB-induced defects play a beneficial role in promoting the diffusion process by providing fast diffusion paths for elements.The optimal joints with the maximum shear strength of 213.7 MPa were obtained through bonding M-Cu and M-CuW at 900℃ and 5 MPa for 30 min,which attributes to the combined effects of fine-grained strengthening and solid solution strengthening.Overall,the application of HCPEB modification showcases its effectiveness in promoting element diffusion and enhancing the mechanical performance of the joints.

关键词： HCPEB Element diffusion Shear strength Crystal defects Surface modification

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How Does Urban Shrinkage Affect Land Use Efficiency?A Case Study of Shrinking Cities in Northeast China

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Chinese Geographical Science 2024年第1期34卷 34-51页

作者： XIE Mingke feng Zhangxian SONG Yang guan Haoming WANG Shijun School of Geographical Sciences Northeast Normal UniversityChangchun130024China

The effect of urban shrinkage has gradually become a new topic.Theoretically,urban shrinkage may exert great influence on land use efficiency(LUE)through various urban subsystems,but there is currently limited research examining these pathways.Using the Super-SBM-Undesirable model and the Structural Equation Model(SEM),this study calculates the LUE of shrinking cities in Northeast China and simulates the process of urban shrinkage affecting LUE.To quantify the process of urban shrinkage affecting LUE,three mediation variables,namely the economy,public services,and innovation,are used as latent variables to apply SEM.The results show that urban shrinkage will affect LUE through a direct path and indirect paths.In the direct path,urban shrinkage leads to an improvement in LUE.In the indirect paths,the economy and innovation will transmit the negative effect of urban shrinkage on LUE,while public services will reverse this effect.An important contribution of this study is that it quantifies the paths of urban shrinkage affecting LUE,thereby expanding the understanding of urban shrinkage effect and laying a foundation for the sustainable development of shrinking cities.

关键词： urban shrinkage land use efficiency Super-SBM-Undesirable model Structural Equation Model(SEM) Northeast China

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