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Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2685-2697页

作者： Fangyan Gao Yueyao Wu Runtian Wang Yuhui Yao Yiqiu Liu Lingling Fan Jingtong Xu Jian Zhang Xin Han Xiaoxiang Guan Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Collaborative Innovation center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Department of Oncology the Second Hospital of NanjingNanjing University of Chinese MedicineNanjing 210023China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains ***,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in *** using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive *** combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,***,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and *** HA-modified nanosystem managed targeted activation via pH/glutathione ***&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a ***,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.

关键词： Triple-negative breast cancer Androgen receptor Checkpoint kinase 1 Enzalutamide MK-8776 Synergy HMnO_(2) Nanodrug delivery system

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Enhancing osteogenic bioactivities of coaxial electrospinning nanoscaffolds through incorporating iron oxide nanoparticles and icaritin for bone regeneration

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Nano Research 2024年第7期17卷 6430-6442页

作者： Peng Wang Qianjin Wang Dengxian Wu Yunyang Zhang Shixiong Kang Xucai Wang Jiayu Gu Hao Wu Zhihong Xu Qing Jiang School of Biomedical Engineering and Informatics Nanjing Medical UniversityNanjing 211166China State Key Laboratory of Pharmaceutical Biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China center of Modem Analysis Nanjing UniversityNanjing 210008China State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210009China Co-Innovation center for Efficient Processing and Utilization of Forest Resources College of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China Jiangsu Institute of Metrology Nanjing 210023China

Bone tissue engineering provides a promising strategy for the treatment of bone ***,the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive ***,we proposed to endow nano-scaffold(NS)constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles(IONPs)and icaritin(ICA).Four types of nano-scaffolds(NS,ICA@NS,NS-IONPs and ICA@NS-IONPs)were *** incorporation of ICA and IONPs minimally impact their surface morphological and chemical *** enhanced the mechanical properties of NS scaffolds,including hardness,tensile strength,and elastic *** vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase(ALP)activity level,expressions of osteogenesis-related genes and proteins as well as mineralized nodule *** investigations revealed that MEK/ERK(MAP kinase-ERK kinase(MEK)/extracellularsignal-regulated kinase(ERK))signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@***,the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone ***,IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.

关键词： iron oxide nanoparticles icaritin coaxial electrospinning nano-scaffolds MEK/ERK signaling pathway bone regeneration

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Network Evolution Analysis of Vehicle Road-Driving Behavior Strategies and Design of Information Guidance Algorithm

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Journal of Social Computing 2024年第1期5卷 58-87页

作者： Tong Lyu Lefeng Shi Weijun He College of Economics and Management China Three Gorges UniversityYichang 443002China National center for applied mathematics in Chongqing Chongqing Normal UniversityChongqing 401331China

By analyzing the influence of time and safety factors on the behavior strategies of vehicles on the road,a network game evolution model between drivers that considers the behavior strategies of the driving vehicle itself and its neighbors is constructed,and the competition relationship between different types of cars is *** influence of the proportion of driving vehicle types on the potential risk of the road is also *** paper presents a guidance algorithm for vehicle dynamic behavior preference *** correctness of the algorithm is verified by an *** shows:The choice of behavior strategies,such as speeding and lane changing,is related to the expected benefits of time,safety,and neighboring vehicle strategies,and the critical value of payable benefits is *** higher the proportion of aggressive vehicles on the road,the greater the potential risk on the *** there is a vehicle in the adjacent lane of the driving vehicle will affect the type of driving *** guidance helps to stabilize the state of vehicles on the road,and the policy transition probability also helps stabilize the form of vehicles cars on the ***,information guidance has a more significant impact on the transition of vehicle ***,the guidance strategy of managers is given when the road is smooth and congested.

关键词： user portrait information guidance network game risk appetite

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Which Neighborhoods Have Easier Access to Online Home Delivery Services?A Spatiotemporal Accessibility Analysis in nanjing,China

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Chinese Geographical Science 2024年第4期34卷 722-738页

作者： KONG Yu ZHEN Feng ZHANG Shanqi SHEN Lizhen School of Architecture and Urban Planning Nanjing UniversityNanjing 210093China Provincial Engineering Research center of Smart City Planning and Digital Governance Nanjing 210093China

The rise in online home delivery services(OHDS)has had a significant impact on how urban services are supplied and used in recent *** on the spatial accessibility of OHDS are emerging,but few is known about the temporal dimension of OHDS accessibility as well as the geographic and socioeconomic differences in the spatiotemporal accessibility of *** study measures the spatiotemporal accessibility of four types of OHDS,namely leisure,fresh and convenient,medical,and catering *** geographic and socioeconomic disparities in the spatiotemporal accessibility of these four types of OHDS are then identified using spatial statistical methods and the Kruskal-Wallis test(K-W test).The case study in nanjing,China,suggests that:1)spatiotemporal accessibility better reflects the temporal variation of OHDS accessibility and avoids overestimation of OHDS accessibility when only considering its spatial dimension.2)The spatiotemporal accessibility of OHDS varies geographically and *** located in the main city or neighborhoods with higher housing prices,higher population density,and higher point of interest(POI)mix have better OHDS spatiotemporal *** study contributes to the understanding of OHDS accessibility from a spatiotemporal perspective,and the empirical insights can assist policymakers in creating intervention plans that take into account variations in OHDS spatiotemporal accessibility.

关键词： online home delivery services(OHDS) spatiotemporal accessibility neighborhoods accessibility differences nanjing City China

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Evaluation and Influencing Factors on Particle Agglomeration in RAP

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Journal of Wuhan University of Technology(Materials Science) 2024年第1期39卷 60-68页

作者：唐伟李宁 ZHUANG Yuan ZHAN He YU Xin WU Wenxiu DING Gongying College of Civil and Transportation Engineering Hohai UniversityNanjing 210098China Jiangsu Expressway Engineering Maintenance Technology center Nanjing 211106China Jinhua Highway and Transportation Management center Jinhua 321000China

Asphalt extraction test and scanning electron microscopy(SEM) were used for analysis of agglomerations of reclaimed asphalt pavement(RAP) particles. In order to quantify the agglomeration degree of RAP, the fineness modulus ratio(FMR) and the percentage loss index(PLI) were proposed. In addition, grey correlation analysis was conducted to discuss the relationship between particle agglomerations and RAP size,asphalt content(AC), and surface area. Two indexes indicate that the agglomeration degree increases in general as the RAP size reduces. This can be attributed to that particles are prone to agglomeration in the case of higher AC. Based on the SEM images and the material composition of RAP, the particle agglomeration in RAP can be classified into weak agglomeration and strong agglomeration. Grey correlation analysis shows that AC is the crucial factor affecting the agglomeration degree and RAP variability. In order to produce consistent and stable reclaimed mixtures, disposal measures of RAP are suggested to lower the AC of RAP.

关键词： RAP particle agglomeration grey correlation analysis asphalt content

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Exploring Long-Memory Process in the Prediction of Interval-Valued Financial Time Series and Its Application

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Journal of Systems Science & Complexity 2024年第2期37卷 759-775页

作者： SHEN Tingting TAO Zhifu CHEN Huayou School of Economics Anhui UniversityHefei 230601China center for Financial and Statistical Research Anhui UniversityHefei 230061China Stony Brook Institute at Anhui University Anhui UniversityHefei 230601China center for applied mathematics Anhui UniversityHefei 230601China

Long-memory process has been widely studied in classical financial time series analysis,which has merely been reported in the field of interval-valued financial time *** aim of this paper is to explore long-memory process in the prediction of interval-valued time series(IvTS).To model the long-memory process,two novel interval-valued time series prediction models named as interval-valued vector autoregressive fractionally integrated moving average(IV-VARFIMA)and ARFIMAX-FIGARCH were *** the developed long-memory pattern,both of the short term and long-term influences contained in IvTS can be *** an application of the proposed models,interval-valued form of WTI crude oil futures price series is *** to current IvTS prediction models,IV-VARFIMA and ARFIMAX-FIGARCH can provide better in-sample and out-of-sample forecasts.

关键词： ARFIMAX-FIGARCH interval-valued time series IV-VARFIMA long-memory process WTI crude oil futures price

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A Generic Strategy to Create Mechanically Interlocked Nanocomposite/Hydrogel Hybrid Electrodes for Epidermal Electronics

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Nano-Micro Letters 2024年第5期16卷 120-133页

作者： Qian Wang Yanyan Li Yong Lin Yuping Sun Chong Bai Haorun Guo Ting Fang Gaohua Hu Yanqing Lu Desheng Kong College of Engineering and applied Sciences National Laboratory of Solid State Microstructureand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210023People’s Republic of China State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjing 210023People’s Republic of China College of Chemical Engineering and Technology Engineering Research Center of Seawater Utilization Technology of Ministry of EducationState Key Laboratory of Reliability and Intelligence of Electrical EquipmentHebei University of TechnologyTianjin 300130People’s Republic of China Key Laboratory of Intelligent Optical Sensing and Manipulation Nanjing UniversityNanjing 210093People’s Republic of China

Stretchable electronics are crucial enablers for next-generation wearables intimately integrated into the human *** the primary compliant conductors used in these devices,metallic nanostructure/elastomer composites often struggle to form conformal contact with the textured *** electrodes have been consequently developed based on conductive nanocomposite and soft hydrogels to establish seamless skin-device ***,chemical modifications are typically needed for reliable bonding,which can alter their original *** overcome this limitation,this study presents a facile fabrication approach for mechanically interlocked nanocomposite/hydrogel hybrid *** this physical process,soft microfoams are thermally laminated on silver nanowire nanocomposites as a porous interface,which forms an interpenetrating network with the *** microfoam-enabled bonding strategy is generally compatible with various *** resulting interlocked hybrids have a 28-fold improved interfacial toughness compared to directly stacked *** electrodes achieve firm attachment to the skin and low contact impedance using tissue-adhesive *** have been successfully integrated into an epidermal sleeve to distinguish hand gestures by sensing mus-cle *** nanocomposite/hydrogel hybrids reported here offer a promising platform to combine the benefits of both materials for epidermal devices and systems.

关键词： Stretchable electronics Epidermal electronics Silver nanowire Conductive nanocomposites Hydrogel

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LSM14B coordinates protein component expression in the P-body and controls oocyte maturation

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Journal of Genetics and Genomics 2024年第1期51卷 48-60页

作者： Huiru Zhang Tao Zhang Xiang Wan Chang Chen Shu Wang Dongdong Qin Lufan Li Luping Yu Xin Wu State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjingJiangsu 210029China center for Reproductive Medicine and Obstetrics and Gynecology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsu 210029China

The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be ***,we demonstrate that Smith-like(LSM)family member 14B(LSM14B)regulates oocyte maturation,and the loss of LSM14B in mouse ovaries leads to abnormal oocyte MII arrest and female ***,we find the aberrant transcriptional activation,indicated by abnormal non-surrounded nucleolus and surrounded nucleolus oocyte proportions,and abnormal chromosome assembly and segregation in Lsm14b-deficient mouse *** global transcriptome analysis suggests that many transcripts involved in cytoplasmic processing body(P-body)function are altered in Lsm14b-deficient mouse *** of Lsm14b results in the expression and/or localization changes of P-body components(such as LSM14A,DCP1A,and 4E-T).Notably,DDX6,a key component of the P-body,is downregulated and accumulates in the nuclei in Lsm14b-deficient mouse *** together,our data suggest that LSM14B links mouse oocyte maturation to female fertility through the regulation of the P-body.

关键词： LSM14B P-body DDX6 MIl arrest Chromatin configuration

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Quantum Neural Network for Quantum Neural Computing

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Research 2024年第1期2023卷 71-80页

作者： Min-Gang Zhou Zhi-Ping Liu Hua-Lei Yin Chen-Long Li Tong-Kai Xu Zeng-Bing Chen National Laboratory of Solid State Microstructures School of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China MatricTime Digital Technology Co.Ltd. Nanjing 211899China

Neural networks have achieved impressive breakthroughs in both industry and *** to effectively develop neural networks on quantum computing devices is a challenging open ***,we propose a new quantum neural network model for quantum neural computing using(classically controlled)single-qubit operations and measurements on real-world quantum systems with naturally occurring environment-induced decoherence,which greatly reduces the difficulties of physical *** model circumvents the problem that the state-space size grows exponentially with the number of neurons,thereby greatly reducing memory requirements and allowing for fast optimization with traditional optimization *** benchmark our model for handwritten digit recognition and other nonlinear classification *** results show that our model has an amazing nonlinear classification ability and robustness to ***,our model allows quantum computing to be applied in a wider context and inspires the earlier development of a quantum neural computer than standard quantum computers.

关键词： quantum thereby breakthrough

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Recombination and repeat-induced point mutation landscapes reveal trade-offs between the sexual and asexual cycles of Magnaporthe oryzae

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Journal of Genetics and Genomics 2024年第7期51卷 723-734页

作者： Xifang Zong Yaxin Lou Mengshuang Xia Kunyang Zhao Jingxuan Chen Ju Huang Sihai Yang Long Wang State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjingJiangsu 210000China State Key Laboratory for Crop Genetics and Germplasm Enhancement Bioinformatics CenterAcademy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjingJiangsu 210000China Co-Innovation center for Sustainable Forestry in Southern China Nanjing Forestry UniversityNanjingJiangsu 210000China

The fungal disease caused by Magnaporthe oryzae is one of the most devastating diseases that endanger many crops *** shows that sexual reproduction can be advantageous for fungal diseases as hybridization facilitates ***,the pervasive clonal lineages of *** observed in natural fields contradict this expectation.A better understanding of the roles of recombination and the fungi-specific repeat-induced point mutation(RIP)in shaping its evolutionary trajectory is essential to bridge this knowledge *** we systematically investigate the RIP and recombination landscapes in *** using a whole genome sequencing data from 252 population samples and 92 cross *** data reveal that the RIP can robustly capture the population history of ***,and we provide accurate estimations of the recombination and RIP rates across different *** ***,our results highlight a parent-of-origin bias in both recombination and RIP rates,tightly associating with their sexual potential and variations of effector *** bias suggests a critical trade-off between generating novel allelic combinations in the sexual cycle to facilitate host-jumping and stimulating transposon-associated diversification of effectors in the asexual cycle to facilitate host *** findings provide unique insights into understanding the evolution of blast fungus.

关键词： Magnaporthe oryzae Crossover Repeat-induced point mutation(RiP) Effectors Sexual reproduction

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