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Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3931-3948页

作者： Fu, Wenkang Lin, Yanyan Bai, Mingzhen Yao, Jia Huang, Chongfei Gao, Long Mi, Ningning Ma, Haidong Tian, Liang Yue, Ping Zhang, Yong Zhang, Jinduo ren, yanxian Ding, Liyun Dai, Lunzhi Leung, Joseph W. Yuan, Jinqiu Zhang, Wenhua Meng, Wenbo Lanzhou Univ Sch Clin Med 1 Lanzhou 730030 Peoples R China Lanzhou Univ Hosp 1 Key Lab Biotherapy & Regenerat Med Gansu Prov Lanzhou 730000 Gansu Peoples R China Lanzhou Univ Hosp 1 Dept Gen Surg Lanzhou 730030 Peoples R China Lanzhou Univ Sch Phys Sci & Technol Lanzhou 730000 Peoples R China Sichuan Univ West China Hosp Natl Clin Res Ctr Geriatr Chengdu 610041 Peoples R China Sichuan Univ West China Hosp Dept Gen Practice State Key Lab Biotherapy Chengdu 610041 Peoples R China UC Davis Med Ctr Div Gastroenterol Sacramento CA 95817 USA Sacramento VA Med Ctr Sacramento CA 95817 USA Sun Yat Sen Univ Affiliated Hosp 7 Clin Res Ctr Big Data Ctr Shenzhen 518107 Guangdong Peoples R China Lanzhou Univ Sch Life Sci Lanzhou 730000 Peoples R China

Cholangiocarcinoma (CCA) is a bile duct malignancy with a dismal prognosis. This study systematically investigated the role of the ribosomal protein S6 ( RPS6 ) gene, which is dependent in CCA. We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis. Functional investigations have shown that alterations in RPS6 expression, both gain- and loss-of function could affect the proliferation of CCA cells. In xenograft tumor models, RPS6 overexpression enhances tumorigenicity, whereas RPS6 silencing reduces it. Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle, especially DNA replication. Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6. Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing (AS) events, and combined with RNA immunoprecipitation sequencing, revealed that minichromosome maintenance complex component 7 ( MCM7 ) binds to RPS6, which regulates its AS and increases oncogenic activity in CCA. Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer (V-PMO) significantly inhibited the growth of CCA cells, patient-derived organoids, and subcutaneous xenograft tumor. Taken together, the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

关键词： Cholangiocarcinoma Ribosomal protein S6 Alternative splicing p53 Minichromosome maintenance complex component 7 Vivo morpholino Patient-derived organoids PROTEIN S6 PHOSPHORYLATION PRE-MESSENGER-RNA EXPRESSION CANCER BINDING BIOGENESIS ACTIVATION GENERATION IMPAIRMENT THERAPIES

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mtDNA-triggered pH response signal-amplified fluorescent probe for multiple cell discrimination

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Chinese Chemical Letters 2024年第3期35卷 363-368页

作者： Tianping Xia yanxian Hou Zhuoran Xia Gengwen Chen Peichen Tang Jiangli Fan Xiaojun Peng State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical EngineeringDalian University of TechnologyDalian 116024China Hematology Reagent R&D Department Mindray Bio-medical Electronics Co.Ltd.Shenzhen 518132China Research Institute of Dalian University of Technology in Shenzhen Shenzhen 518057China

Developing fluorescence probes with multiple responses has vital significance but remains ***,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell *** probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic *** the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor *** study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.

关键词： Fluorescence probe Mitochondrial DNA pH response Peripheral blood cells Multiple cell detection

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Instantaneous preparation of gold-carbon dot nanocomposites for on-site SERS identification of pathogens in diverse interfaces

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Photonics Research 2024年第6期12卷 1303-1312页

作者： yanxian GUO YE LIU CHAOCAI LUO YUE ZHANG YANG LI FEI ZHOU ZHOUYI GUO ZHENGFEI ZHUANG ZHIMING LIU School of Electronic Engineering and Intelligentization Dongguan University of TechnologyDongguan 523808China Department of Physics University of Science and Technology of ChinaHefei 230026China MOE Key Laboratory of Laser Life Science&Guangdong Provincial Key Laboratory of Laser Life Science College of BiophotonicsSouth China Normal UniversityGuangzhou 510631China

Rapid detection of pathogens present on contaminated surfaces is crucial for food safety and public health due to the high morbidity and mortality of bacterial ***,a sensitive and efficient method for on-site identification of foodborne pathogens on anisotropic surfaces was developed by using an in situ instantaneously prepared surface-enhanced Raman scattering(SERS)*** achieve this,molybdenum-doped gallic acidderived carbon dots(MCDs)are utilized as the reductant for synthesizing Au@MCDs nanohybrids within just 3 s at ambient *** synergistic effect of the electromagnetic enhancement and charge transfer of Au@MCDs enables excellent SERS performance 10 times stronger than bare Au *** bioassay platform requires less than 5 min to complete the quantitative detection of foodborne pathogens on various microbial-contaminated interfaces with a sensitivity of 10 CFU/m *** innovative strategy breaks the long-standing limitations of SERS substrates in practical use,such as the time-consuming process,interference of residual surfactants,poor surface stability,and few application scenarios,providing a promising tool for widespread applications in biomedical research and clinical diagnostics.

关键词： temperature molybdenum consuming

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Local coordination and electronic interactions of Pd/MXene via dual‐atom codoping with superior durability for efficient electrocatalytic ethanol oxidation

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Carbon Energy 2024年第8期6卷 166-177页

作者： Zhangxin Chen Fan Jing Minghui Luo Xiaohui Wu Haichang Fu Shengwei Xiao Binbin Yu Dan Chen Xianqiang Xiong yanxian Jin School of Pharmaceutical and Chemical Engineering Taizhou UniversityTaizhouZhejiangChina School of Sciences Zhejiang Sci‐Tech UniversityHangzhouZhejiangChina

Catalyst design relies heavily on electronic metal‐support interactions,but the metal‐support interface with an uncontrollable electronic or coordination environment makes it ***,we outline a promising approach for the rational design of catalysts involving heteroatoms as anchors for Pd nanoparticles for ethanol oxidation reaction(EOR)*** doped B and N atoms from dimethylamine borane(DB)occupy the position of the Ti_(3)C_(2)lattice to anchor the supported Pd *** electrons transfer from the support to B atoms,and then to the metal Pd to form a stable electronic center.A strong electronic interaction can be produced and the d‐band center can be shifted down,driving Pd into the dominant metallic state and making Pd nanoparticles deposit uniformly on the ***‐obtained Pd/DB–Ti_(3)C_(2)exhibits superior durability to its counterpart(∼14.6%retention)with 91.1%retention after 2000 cycles,placing it among the top single metal anodic ***,in situ Raman and density functional theory computations confirm that Pd/DB–Ti_(3)C_(2)is capable of dehydrogenating ethanol at low reaction energies.

关键词： durability electronic interactions ethanol oxidation heteroatom codoping Pd/MXene

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A FAS approach for stabilization of generalized chained forms: part 1. Discontinuous control laws

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Science China(Information Sciences) 2024年第2期67卷 118-143页

作者： Guang-ren DUAN Center for Control Theory and Guidance Technology Harbin Institute of Technology Center for Control Science and Technology Southern University of Science and Technology

In this paper, a type of general nonholonomic systems is proposed, which contains both the Brockett’s two example systems, and their extended n-dimensional chained forms, as special cases. For the stabilization of such systems, a stabilizing controller is proposed based on the fully actuated system(FAS)approach, which is discontinuous at the origin but time-invariant when the open-loop system is time-invariant,and drives the feasible trajectories of the system to the origin exponentially. Furthermore, the proposed FAS approach is also extended to the sub-normal system case and the time-delay system case.

关键词： nonholonomic systems feedback stabilization exponential convergence sub-fully actuated systems time-delay systems

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A FAS approach for stabilization of generalized chained forms: part 2. Continuous control laws

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Science China(Information Sciences) 2024年第3期67卷 114-135页

作者： Guang-ren DUAN Center for Control Theory and Guidance Technology Harbin Institute of Technology Shenzhen Key Laboratory of Control Theory and Intelligent Systems Southern University of Science and Technology

In this paper, continuous time-varying stabilizing controllers for the type of general nonholonomic systems proposed and treated in part 1 are designed using the fully actuated system(FAS) approach. The key step is to differentiate the first scalar equation, and by control of the obtained second-order scalar system, a proportional plus integral feedback form for the first control variable is obtained. With the solution to this designed second-order scalar system, the rest equations in the nonholonomic system form an independent time-varying subsystem which is then handled by the FAS approach. The overall designed controller contains an almost arbitrarily chosen design parameter, and is proven to guarantee the uniformly and globally exponential stability of the closed-loop system. The proposed approach is simple and effective,and is demonstrated with a practical example of ship control.

关键词： nonholonomic systems feedback stabilization fully actuated systems Lyapunov stability continuous controllers

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Resilient control of flexible hypersonic vehicles against unmatched distributed faults

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Chinese Journal of Aeronautics 2024年第5期37卷 60-70页

作者： Dong ZHAO Wenjing ren School of Artificial Intelligence Anhui UniversityHefei 230601China Key Laboratory of System Control and Information Processing Ministry of EducationShanghai Jiao Tong UniversityShanghai 200240China School of Electrical Engineering and Automation Hefei University of TechnologyHefei 230009China

This paper studies a robust fault compensation and vibration suppression problem of flexible hypersonic *** controlled plant is represented by a cascade system composed of a nonlinear Ordinary Differential Equation(ODE)and an Euler-Bernoulli Beam Equation(EBBE),in which the vibration dynamics is coupled with the rigid dynamics and suffers from distributed faults.A state differential transformation is introduced to transfer distributed faults to an EBBE boundary and a longitudinal dynamics is refined by utilizing T-S fuzzy IF-THEN rules.A novel T-S fuzzy based fault-tolerant control algorithm is developed and related stability conditions are *** robust exponential stability and well-posedness are proved by using the modified l_(0)-semigroup based Lyapunov direct approach.A simulation study on the longitudinal dynamics of flexible hypersonic vehicles effectively verifies the validity of the developed theoretical results.

关键词： Flexible hypersonic vehicles ODE-EBBE cascade Robust exponential stability Unmatched distributed fault compensation Vibration suppression

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Progress in modeling and control of probe-and-drogue autonomous aerial refueling

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Chinese Journal of Aeronautics 2024年第5期37卷 6-26,I0001页

作者： Jinrui ren Quan QUAN School of Automation Xi’an University of Posts&TelecommunicationsXi'an 710072China School of Automation Science and Electrical Engineering Beihang UniversityBeijing 100191China

By refueling aircraft while they are in flight,aerial refueling is an efficient technique to extend their endurance and *** Aerial Refueling(AAR)is anticipated to be used to complete aerial refueling for unmanned *** are three aerial refueling methods:the Probe-and-Drogue Refueling(PDR)refueling method,the flying-boom refueling method,and the boom-drogue-adapter refueling *** paper considers the PDR approach,the most challenging of the three,because the flexible hose-drogue assembly has fast dynamics and is susceptible to various kinds of winds,which makes the probe docking with the drogue *** is divided into four phases,namely the rendezvous phase,joining phase,refueling phase,and reform phase,with the refueling phase being the most *** controller design faces the greatest challenge during the docking control of the refueling phase since it calls for a high level of safety,precision,and *** a result,the modeling and control issues encountered during the refueling phase are typical and *** fundamental idea of AAR is presented in the paper first,after which the characteristics and requirements of AAR are *** progress in modeling and control techniques for the AAR’s refueling phase is then systematically ***,potential future work for high safety,precision,and efficiency requirements is examined and suggested.

关键词： Aerial refueling Probe-and-drogue refueling Docking Flight controlsystems Unmanned Aerial Vehicles

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Nonlocal symmetries,soliton-cnoidal wave solution and soliton molecules to a(2+1)-dimensional modified KdV system

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Communications in Theoretical Physics 2024年第4期76卷 14-21页

作者： Jianyong Wang Bo ren Department of Mathematics and Physics Quzhou UniversityQuzhou 324000China Department of Mathematics Zhejiang University of TechnologyHangzhou 310014China

A(2+1)-dimensional modified KdV(2DmKdV)system is considered from several ***,residue symmetry,a type of nonlocal symmetry,and the Bäcklund transformation are obtained via the truncated Painlevéexpansion ***,the residue symmetry is localized to a Lie point symmetry of a prolonged system,from which the finite transformation group is ***,the integrability of the 2DmKdV system is examined under the sense of consistent tanh expansion ***,explicit soliton-cnoidal wave solutions are ***,abundant patterns of soliton molecules are presented by imposing the velocity resonance condition on the multiple-soliton solution.

关键词： soliton-cnoidal wave solution nonlocal symmetry soliton molecule (2+1)-dimensional modified KdV system

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Global Solvability for a Predator-Prey Model with Prey-Taxis and Rotational Flux Terms

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Chinese Annals of Mathematics,Series B 2024年第2期45卷 297-318页

作者： Guoqiang ren Bin LIU School of Mathematics and Statistics Huazhong University of Science and Technology Hubei Key Laboratory of Engineering Modeling and Scientific Computing Huazhong Universityof Science and Technology

In this paper the author investigates the following predator-prey model with prey-taxis and rotational?ux terms■in a bounded domain with smooth *** presents the global existence of generalized solutions to the model... 详细信息

关键词： Predator-prey Prey-taxis Giopal existence Kotational flnux

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