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EGFR-targeted and gemcitabine-incorporated chemogene for combinatorial pancreatic cancer treatment

Nano Research 2024年第2期17卷 848-857页

作者： Miao Xie Qiushuang Zhang Yuanyuan guo Lijuan zhu Xinyuan zhu Chuan Zhang School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesInstitute of Molecular MedicineSixth people’s HospitalSchool of MedicineShanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong UniversityShanghai 200240China Department of Radiology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200233China Institute of Molecular Medicine Shanghai Jiao Tong University Affiliated Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Pancreatic cancer stands out as a recognized intractable tumor due to its high malignancy and mortality rates,which are largely attributed to the insensitivity of current clinical chemotherapies or *** chemo and gene therapy that integrates different therapeutic targets,may increase the chemosensitivity of pancreatic cancer and synergistically enhance the antitumor ***,conventional co-delivery of gene and chemo drugs is intensively dependent on complex nanoparticle delivery systems,thus would be limited by unstable drug packaging,nonspecific biodistribution,and biosafety ***,we rationally designed an epidermal growth factor-receptor(EGFR)-targeted and gemcitabine-incorporated oligonucleotide(termed as chemogene)with anti-Bcl-2 sequence,which achieves simple and precise integration of gemcitabine into a gene regulative agent,as well as the EGFR-targeted delivery for pancreatic cancer *** solid-phase synthesis,gemcitabine,as the first-line chemodrug for pancreatic cancer,is introduced to the antisense oligonucleotide to replace all cytosine nucleosides to obtain the gemcitabine-integrated chemogene(Ge-ASO^(Bcl-2)).Thereafter,Ge-ASO^(Bcl-2)is covalently coupled with EGFR nanobody to construct the final targeted chemogene without any exogenous ***,this nanobody-conjugated chemogene exhibits remarkable tumor targeting capability and antitumor effects both in vitro and in vivo,which initiates a first step toward the application of combinatorial chemo and gene therapy for future pancreatic cancer treatment.

关键词： antisense oligonucleotide chemogene nanobody drug delivery system pancreatic cancer

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A condition-based maintenance policy for reconfigurable multi-device systems

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Advances in Manufacturing 2024年第2期12卷 252-269页

作者： Shu-Lian Xie Feng Xue wei-Min Zhang Jia-wei zhu School of Mechanical Engineering Tongji UniversityShanghai201804People’s Republic of China

The exploration of component states for optimizing maintenance schedules in complex systems has garnered significant interest from ***,current literature usually overlooks the critical aspects of system flexibility and *** implementation of system reconfiguration can effectively mitigate system downtime and enhance production *** study proposes a dynamic condition-based maintenance policy considering reconfiguration for reconfigurable systems.A double-layer decision rule was constructed for the devices and *** achieve the best overall maintenance effect of the system,the remaining useful life probability distribution and recommended maintenance time of each device were used to optimize the concurrent maintenance time window of the devices and determine whether to reconfigure them.A comprehensive maintenance efficiency index was introduced that simultaneously considered the maintenance cost rate,reliability,and availability of the system to characterize the overall maintenance *** reconfiguration cost was included in the maintenance *** proposed policy was tested through numerical experiments and compared with different-level *** results show that the proposed policy can significantly reduce the downtime and maintenance costs and improve the overall system reliability and availability.

关键词： Condition-based maintenance(CBM) Reconfigurable system Remaining useful life Maintenance cost System reliability

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IMAGE SUPER-RESOLUTION RECONSTRUCTION BY HUBER REGULARIZATION AND TAILORED FINITE POINT METHOD

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Journal of Computational Mathematics 2024年第2期42卷 313-336页

作者： Wenli Yang Zhongyi Huang wei zhu School of Mathematics China University of Mining and TechnologyXuzhou 221116China Department of Mathematics Tsinghua UniversityBeijing 100084China Department of Mathematics University of AlabamaTuscaloosaAL 35487USA

In this paper,we propose using the tailored finite point method(TFPM)to solve the resulting parabolic or elliptic equations when minimizing the Huber regularization based image super-resolution model using the augmented Lagrangian method(ALM).The Hu-ber regularization based image super-resolution model can ameliorate the staircase for restored *** employs the method of weighted residuals with collocation tech-nique,which helps get more accurate approximate solutions to the equations and reserve more details in restored *** compare the new schemes with the Marquina-Osher model,the image super-resolution convolutional neural network(SRCNN)and the classical interpolation methods:bilinear interpolation,nearest-neighbor interpolation and bicubic *** experiments are presented to demonstrate that with the new schemes the quality of the super-resolution images has been *** these,the existence of the minimizer of the Huber regularization based image super-resolution model and the convergence of the proposed algorithm are also established in this paper.

关键词： Image super-resolution Variational model Augmented Lagrangian methods Tailored finite point method

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The repression of oncoprotein SET by the tumor suppressor p53 reveals a p53-SET-PP2A feedback loop for cancer therapy

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Science China(Life Sciences) 2023年第1期66卷 81-93页

作者： Han Yao Wenbin Xu Yajing Liu Zhijie Cao Jia Wen Mi Zhang Zhen Wu Xiaojun Yan Zishan Jiao Zijing Zhang Jianyuan Chen Meng Zhang wei-guo zhu Donglai Wang State Key Laboratory of Medical Molecular Biology&Department of Medical Genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Anatomy Histology and EmbryologySchool of Basic MedicineChina Medical UniversityShenyang 110122China Department of Biochemistry and Molecular Biology Shenzhen University School of MedicineShenzhen 518060China

The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms,including the hijacking of the tumor suppressors p53 and *** aberrant SET represents a promising strategy for cancer ***,the mechanism by which endogenous SET is regulated in cancer cells remains largely ***,we identified the tumor suppressor p53 as a key regulator that transcriptionally repressed the expression of SET in both normal and cancer *** addition,p53 stimulated PP2A phosphatase activity via p53-mediated transcriptional repression of SET,whereby SET-mediated inhibition of PP2A was ***,targeting the interaction between SET and PP2A catalytic subunit(PP2Ac)with FTY720 enhanced stress-induced p53 activation via PP2A-mediated dephosphorylation of p53 on threonine 55(Thr55).Therefore,our findings uncovered a previously unknown p53-SETPP2A regulatory feedback *** functionally potentiate this feedback loop,we designed a combined therapeutic strategy by simultaneously administrating a p53 activator and SET antagonist in cancer cells and observed a dramatic synergistic effect on tumor *** study reveals mechanistic insight into the regulation of the oncoprotein SET and raises a potential strategy for cancer therapy by stimulating the p53-SET-PP2A feedback loop.

关键词： p53 SET PP2A FTY720 feedback loop tumor suppression

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Gas–solid reactor optimization based on EMMS-DPM simulation and machine learning

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Particuology 2024年第6期89卷 131-143页

作者： Haolei Zhang Aiqi zhu Ji Xu wei Ge State Key Laboratory of Mesoscience and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

Design,scaling-up,and optimization of industrial reactors mainly depend on step-by-step experiments and engineering experience,which is usually time-consuming,high cost,and high *** numerical simulation can reproduce high resolution details of hydrodynamics,thermal transfer,and reaction process in reactors,it is still challenging for industrial reactors due to huge computational *** this study,by combining the numerical simulation and artificial intelligence(AI)technology of machine learning(ML),a method is proposed to efficiently predict and optimize the performance of industrial reactors.A gas–solid fluidization reactor for the methanol to olefins process is taken as an example.1500 cases under different conditions are simulated by the coarse-grain discrete particle method based on the Energy-Minimization Multi-Scale model,and thus,the reactor performance data set is *** develop an efficient reactor performance prediction model influenced by multiple factors,the ML method is established including the ensemble learning strategy and automatic hyperparameter optimization technique,which has better performance than the methods based on the artificial neural ***,the operating conditions for highest yield of ethylene and propylene or lowest pressure drop are searched with the particle swarm optimization algorithm due to its strength to solve non-linear optimization *** show that decreasing the methanol inflow rate and increasing the catalyst inventory can maximize the yield,while decreasing methanol the inflow rate and reducing the catalyst inventory can minimize the pressure *** two objectives are thus conflicting,and the practical operations need to be compromised under different circumstance.

关键词： Discrete particle method Artificial intelligence Machine learning Particle swarm optimization Industrial reactor optimization

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Reconfigurable mechanism-based metamaterials for ternary-coded elastic wave polarizers and programmable refraction control

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Applied Mathematics and Mechanics(English Edition) 2024年第7期45卷 1225-1242页

作者： Zhou HU Zhibo wei Yan CHEN Rui zhu School of Aerospace Engineering Beijing Institute of TechnologyBeijing100081China School of Mechanical Engineering Tianjin UniversityTianjin300350China Key Laboratory of Mechanism Theory and Equipment Design of Ministry of Education Tianjin UniversityTianjin300350China

Elastic metamaterials with unusual elastic properties offer unprecedented ways to modulate the polarization and propagation of elastic ***,most of them rely on the resonant structural components,and thus are frequency-dependent and ***,we present a reconfigurable 2D mechanism-based metamaterial which possesses transformable and frequency-independent elastic *** on the proposed mechanism-based metamaterial,interesting functionalities,such as ternarycoded elastic wave polarizer and programmable refraction,are ***,unique ternary-coded polarizers,with 1-trit polarization filtering and 2-trit polarization separating of longitudinal and transverse waves,are first ***,the strong anisotropy of the proposed metamaterial is harnessed to realize positive-negative bi-refraction,only-positive refraction,and only-negative ***,the wave functions with detailed microstructures are numerically verified.

关键词： elastic metamaterial elastic wave reconfigurable design zero mode ternary code programmable refraction

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Micro-flow structure at regime transition from bubbling to turbulent fluidization in a fluidized bed

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Particuology 2024年第6期89卷 117-130页

作者： Chaoyu Yan Yue Yuan Xiaoyang wei Jesse zhu State Key Laboratory of Heavy Oil Processing Beijing Key Laboratory of Process Fluid Filtration and SeparationCollege of Mechanical and Transportation EngineeringChina University of PetroleumBeijing 102249China China Beacons Institute The University of NottinghamNingbo315100China Department of Chemical and Biochemical Engineering University of Western OntarioLondonOntarioN6A 5B9Canada

Gas-solid fluidized beds have found extensive utilization in frontline manufacturing,in particular as low-velocity *** fluidization status,the bubbling or turbulent flow regime and the transition in between,determine the system performance in practical *** the convoluted hydrodynamics are quantitively evaluated through numerous data-processing methodologies,none of them alone can reflect all the critical information to identify the transition from the bubbling to the turbulent ***,this study was to exploit a coupling data processing methodology,in the combination of standard deviation,power spectrum density,probability density function,wavelet transform,and wavelet multiresolution method,to jointly explain the micro-flow structure at the regime transition from bubbling to turbulent *** transient differential pressure fluctuation was measured for the evaluation in a fluidized bed(0.267 m i.d.×2.5 m height)with FCC catalysts(d_(p)=65μm,ρ_(p)=1780kg/m^(3))at different superficial gas velocities(0.02–1.4 m/s).The results show that the onset of turbulent fluidization starts earlier in the top section of the bed than in the bottom *** wavelet decomposition displays that the fluctuation of differential pressure mainly concentrates on the sub-signals with an intermediate frequency *** sub-signals could be synthesized into three types of scales(micro-scale,meso-scale,and macro-scale),representing the multi-scale hydrodynamics in the fluidized *** micro-scale signal has the characteristic information of bubbling fluidization,and the characteristic information of turbulent fluidization is mainly represented by the meso-scale *** work provides a systematic comprehension of fluidization status assessment and serves as an impetus for more coupling analysis in this sector.

关键词： Flow regime transition Bubbling fluidization Turbulent fluidization Micro-flow structure Differential pressure fluctuation

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Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

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World Journal of Psychiatry 2024年第1期14卷 26-35页

作者： Qi-Fan Huo Li-Juan zhu Jian-wei guo Yan-An Jiang Jing Zhao Department of Anesthesiology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture *** fracture is a common type of fracture in older *** hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint *** To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent *** A total of 397 patients who underwent THA from February 2019 to August *** conducted a three-year retrospective cohort study in Shaanxi Provincial People’s *** demographic data were obtained from the electronic medical record *** collected preoperative,intraoperative,and postoperative *** hundred twenty-nine patients who were administered Dex during the operation were included in the Dex *** hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin *** hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin *** patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were *** There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of th

关键词： Ulinastatin Dexmedetomidine Postoperative cognitive dysfunction Inflammatory cytokines Total hip arthroplasty

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An effective strategy of constructing multi-metallic oxides of ZnO/ CoNiO_(2)/CoO/C microflowers for improved supercapacitive performance

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Chinese Journal of Chemical Engineering 2024年第3期67卷 1-8页

作者： wei guo Yan Zhang Xiaxin Lei Shuang Wang College of Physics Taiyuan University of TechnologyJinzhong 030600China College of Environmental Science and Engineering Taiyuan University of TechnologyJinzhong 030600China Shanxi Key Laboratory of Gas Energy Efficient and Clean Utilization Taiyuan University of TechnologyTaiyuan 030024China

In this work,a new ZnO/CoNiO_(2)/CoO/C metal oxides composite is prepared by cost-effective hydrothermal method coupled with annealing process under N_(2) ***,the oxidation-defect annealing environment is conducive to both morphology and component of the composite,which flower-like ZnO/CoNiO_(2)/CoO/C is *** from good chemical stability of ZnO,high energy capacity of CoNiO_(2) and CoO and good conductivity of C,the as-prepared sample shows promising electrochemical behavior,including the specific capacity of 1435 C·g^(-1) at 1 A·g^(-1),capacity retention of 87.3%at 20 A·g^(-1),and cycling stability of 90.5%for 3000 cycles at 5 A·g^(-1),***,the prepared ZnO/CoNiO_(2)/CoO/C/NF//AC aqueous hybrid supercapacitors device delivers the best specific energy of 55.9 W·h·kg^(-1) at 850 W·kg^(-1).The results reflect that the as-prepared ZnO/CoNiO_(2)/CoO/C microflowers are considered as high performance electrode materials for supercapacitor,and the strategy mentioned in this paper is benefit to prepare mixed metal oxides composite for energy conversion and storage.

关键词： Composites Electrochemistry Hydrothermal Transition metal oxides Structural control Supercapacitors

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Research on Sleeve Grouting Density Detection Based on the Impact Echo Method

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Structural Durability & Health Monitoring 2024年第2期18卷 143-159页

作者： Pu Zhang Yingjun Li Xinyu zhu Shizhan Xu Pinwu Guan wei Liu Yanwei guo Haibo Wang School of Civil Engineering Zhengzhou UniversityZhengzhou450000China Xixi Expressway Construction Co. Ltd.Nanyang474450China

Grouting defects are an inherent challenge in construction practices,exerting a considerable impact on the operational structural integrity of *** investigation employed the impact-echo technique for the detection of grouting anomalies within connections,enhancing its precision through the integration of wavelet packet energy principles for damage identification purposes.A series of grouting completeness assessments were meticulously conducted,taking into account variables such as the divergent material properties of the sleeves and the configuration of adjacent *** findings revealed that:(i)the energy distribution for the highstrength concrete cohort predominantly occupied the frequency bands 42,44,45,and 47,whereas for other groups,it was concentrated within the 37 to 40 frequency band;(ii)the delineation of empty sleeves was effectively discernible by examining the wavelet packet energy ratios across the spectrum of frequencies,albeit distinguishing between sleeves with 50%and full grouting density proved challenging;and(iii)the wavelet packet energy analysis yielded variable detection outcomes contingent on the material attributes of the sleeves,demonstrating heightened sensitivity when applied to ultrahigh-performance concrete matrices and GFRP-reinforced steel bars.

关键词： Prefabricated building steel grouting sleeve impact echo method wavelet packet energy grouted defect

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