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An engineered DNA aptamer-based PROTAC for precise therapy of p53-R175H hotspot mutant-driven cancer

Science Bulletin 2024年第13期69卷 2122-2135页

作者： Lingping Kong Fanlu Meng Ping Zhou Ruixin Ge Xiaoshan Geng Zhihao Yang Guo Li Linlin Zhang Jing Wang Jinfeng Ma Cheng Dong Jun Zhou Sijin Wu Diansheng Zhong Songbo Xie Department of Medical Oncology Tianjin Medical University General HospitalTianjin 300052China Center for Cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinan 250014China The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease(Ministry of Education)School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Haihe Laboratory of Cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai UniversityTianjin 300071China Wisdom Lake Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215028China Department of Ophthalmology Tianjin Medical University General HospitalLaboratory of Molecular OphthalmologyTianjin Key Laboratory of Ocular TraumaTianjin Medical UniversityTianjin 300052China

Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various cancer *** extensive efforts,the absence of a druggable active site for small molecules has rendered these mutants therapeutically *** we develop a selective and effective proteolysis-targeting chimera(PROTAC)for p53-R175H,a common hotspot mutant with dominant-negative and oncogenic *** a novel iterative molecular docking-guided post-SELEX(systematic evolution of ligands by exponential enrichment)approach,we rationally engineer a high-performance DNA aptamer with improved affinity and specificity for *** this resulting aptamer as a binder for PROTACs,we successfully developed a selective p53-R175H degrader,named ***53m induces the ubiquitin–protea some-dependent degradation of p53-R175H while sparing wildtype ***,dp53m demonstrates significant antitumor efficacy in p53-R175H-driven cancer cells both in vitro and in vivo,without ***,dp53m significantly and synergistically improves the sensitivity of these cells to cisplatin,a commonly used chemotherapy *** findings provide evidence of the potential therapeutic value of dp53m in p53-R175H-driven cancers.

关键词： P53 Aptamer PROTAC Cancer Drug resistance

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Probing the peripheral self-generated magnetic field distribution in laser-plasma magnetic reconnection with Martin-Puplett interferometer polarimeter

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Chinese Physics B 2024年第4期33卷 129-134页

作者：张雅芃姚嘉文刘正东马作霖仲佳勇 Department of Astronomy Beijing Normal UniversityBeijing 100875China institute for Frontiers in Astronomy and Astrophysics Beijing Normal UniversityBeijing 102206China

Magnetic reconnection of the self-generated magnetic fields in laser-plasma interaction is an important laboratory method for modeling high-energy density astronomical and astrophysical *** use the Martin-Puplett interferometer(MPI)polarimeter to probe the peripheral magnetic fields generated in the common magnetic reconnection configuration,two separated coplanar plane targets,in laser-target *** introduce a new method that can obtain polarization information from the interference pattern instead of the sinusoidal function fitting of the intensity.A bidirectional magnetic field is observed from the side view,which is consistent with the magneto-hydro-dynamical(MHD)simulation results of self-generated magnetic field *** find that the cancellation of reverse magnetic fields after averaging and integration along the observing direction could reduce the magnetic field strength by one to two orders of *** indicates that imaging resolution can significantly affect the accuracy of measured magnetic field strength.

关键词： laser-plasma experiment polarimeter self-generated magnetic field magnetic reconnection

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Detecting short-term gravitational waves from post-merger hyper-massive neutron stars with a kilohertz detector

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Chinese Physics B 2024年第8期33卷 222-228页

作者：陈奕康朱宗宏 institute for Frontier in Astronomy and Astrophysics Beijing Normal UniversityBeijing 102206China Department of Astronomy Beijing Normal UniversityBeijing 100875China

Gravitational waves emanating from binary neutron star inspirals,alongside electromagnetic transients resulting from the aftermath of the GW170817 merger,have been successfully ***,the intricate post-merger dynamics that bridge these two sets of observables remain *** includes if,and when,the post-merger remnant star collapses to a black hole,and what are the necessary conditions to power a short gamma-ray burst,and other observed electromagnetic *** focus is on the detection of gravitational wave(GW)emissions from hyper-massive neutron stars(NSs)formed through binary neutron star(BNS)*** several kilohertz GW detectors,we simulate BNS mergers within the detection limits of LIGO-Virgo-KARGA *** objective is to ascertain the fraction of simulated sources that may emit detectable post-merger GW *** kilohertz detectors equipped with a new cavity design,we estimate that approximately 1.1%-32%of sources would emit a detectable post-merger GW *** fraction is contingent on the mass converted into gravitational wave energy,ranging from 0.01M_(sun)to 0.1M_(sun).Furthermore,by evaluating other well-regarded proposed kilohertz GW detectors,we anticipate that the fraction can increase to as much as 2.1%-61%under optimal performance conditions.

关键词： neutron star mergers gravitational waves

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Neoantigen cancer vaccines:a new star on the horizon

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Cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling Li Jian You Liping Hong Weijiang Liu Peng Guo Xishan Hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China tianjin Medical university Cancer institute&Hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer *** of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal *** neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint *** made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of ***,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents *** review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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APFA:Ameliorated Pathfinder Algorithm for Engineering Applications

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Journal of Bionic Engineering 2024年第3期21卷 1592-1616页

作者： Keyu Zhong Fen Xiao Xieping Gao Key Laboratory of Computing and Stochastic Mathematics of Ministry of Education Hunan Normal UniversityChangsha410081China School of Mathematics and Statistics Hunan Normal UniversityChangsha410081China School of Computer Science Xiangtan UniversityXiangtan411105China Hunan Provincial Key Laboratory of Intelligent Computing and language Information Processing Hunan Normal UniversityChangsha410081China

Pathfinder algorithm(PFA)is a swarm intelligent optimization algorithm inspired by the collective activity behavior of swarm animals,imitating the leader in the population to guide followers in finding the best food *** algorithm has the characteristics of a simple structure and high ***,PFA faces challenges such as insufficient population diversity and susceptibility to local optima due to its inability to effectively balance the exploration and exploitation *** paper proposes an Ameliorated Pathfinder Algorithm called APFA to solve complex engineering optimization ***,a guidance mechanism based on multiple elite individuals is presented to enhance the global search capability of the ***,to improve the exploration efficiency of the algorithm,the Logistic chaos mapping is introduced to help the algorithm find more high-quality potential solutions while avoiding the worst ***,a comprehensive following strategy is designed to avoid the algorithm falling into local optima and further improve the convergence *** three strategies achieve an effective balance between exploration and exploitation overall,thus improving the optimization performance of the *** performance evaluation,APFA is validated by the CEC2022 benchmark test set and five engineering optimization problems,and compared with the state-of-the-art metaheuristic *** numerical experimental results demonstrated the superiority of APFA.

关键词： Pathfinder algorithm Swarm intelligent Metaheuristic Engineering problems

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An Efficient Multi-objective Approach Based on Golden Jackal Search for Dynamic Economic Emission Dispatch

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Journal of Bionic Engineering 2024年第3期21卷 1541-1566页

Dynamic Economic Emission Dispatch(DEED)aims to optimize control over fuel cost and pollution emission,two conflicting objectives,by scheduling the output power of various units at specific *** many methods well-performed on the DEED problem,most of them fail to achieve expected results in practice due to a lack of effective trade-off mechanisms between the convergence and diversity of non-dominated optimal dispatching *** address this issue,a new multi-objective solver called Multi-Objective Golden Jackal Optimization(MOGJO)algorithm is proposed to cope with the DEED *** proposed algorithm first stores non-dominated optimal solutions found so far into an ***,it chooses the best dispatching solution from the archive as the leader through a selection mechanism designed based on elite selection strategy and Euclidean distance index *** mechanism can guide the algorithm to search for better dispatching solutions in the direction of reducing fuel costs and pollutant ***,the basic golden jackal optimization algorithm has the drawback of insufficient search,which hinders its ability to effectively discover more Pareto *** this end,a non-linear control parameter based on the cosine function is introduced to enhance global exploration of the dispatching space,thus improving the efficiency of finding the optimal dispatching *** proposed MOGJO is evaluated on the latest CEC benchmark test functions,and its superiority over the state-of-the-art multi-objective optimizers is highlighted by performance ***,empirical results on 5-unit,10-unit,IEEE 30-bus,and 30-unit systems show that the MOGJO can provide competitive compromise scheduling solutions compared to published DEED ***,in the analysis of the Pareto dominance relationship and the Euclidean distance index,the optimal dispatching solutions provided by MOGJO are the closest to the ideal solutions for minimizing fuel costs

关键词： Dynamic economic emission dispatch Multi-objective optimization Golden jackal Euclidean distance index

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Text Reasoning Chain Extraction for Multi-Hop Question Answering

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Tsinghua Science and Technology 2024年第4期29卷 959-970页

作者： Pengming Wang Zijiang Zhu Qing Chen Weihuang Dai School of Data Science and Artificial Intelligence Wenzhou University of TechnologyWenzhou 325035China School of Computer Science and also with Institute of Intelligent Information ProcessingSouth China Business CollegeGuangdong University of Foreign StudiesGuangzhou 510545China School of Psychology Jiangxi Normal UniversityNanchang 330022China also with School of Science East China Jiaotong UniversityNanchang 330013China institute of Intelligent Information Processing South China Business CollegeGuangdong University of Foreign StudiesGuangzhou 510545China

With the advent of the information age, it will be more troublesome to search for a lot of relevant knowledge to find the information you need. Text reasoning is a very basic and important part of multi-hop question and answer tasks. This paper aims to study the integrity, uniformity, and speed of computational intelligence inference data capabilities. That is why multi-hop reasoning came into being, but it is still in its infancy, that is, it is far from enough to conduct multi-hop question and answer questions, such as search breadth, process complexity, response speed, comprehensiveness of information, etc. This paper makes a text comparison between traditional information retrieval and computational intelligence through corpus relevancy and other computing methods. The study finds that in the face of multi-hop question and answer reasoning, the reasoning data that traditional retrieval methods lagged behind in intelligence are about 35% worse. It shows that computational intelligence would be more complete, unified, and faster than traditional retrieval methods. This paper also introduces the relevant points of text reasoning and describes the process of the multi-hop question answering system, as well as the subsequent discussions and expectations.

关键词： intelligent computing multi-hop quiz text reasoning document retrieval text complex network

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Meta-path reasoning of knowledge graph for commonsense question answering

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Frontiers of Computer Science 2024年第1期18卷 49-59页

作者： Miao ZHANG Tingting HE Ming DONG National Engineering Research Center for E-Learning Central China Normal UniversityWuhan 430079China Hubei Provincial Key Laboratory of Artificial Intelligence and Smart Learning Central China Normal UniversityWuhan 430079China National language Resources Monitoring&Research Center for Network Media Central China Normal UniversityWuhan 430079China School of Computer Central China Normal UniversityWuhan 430079China

Commonsense question answering(CQA)requires understanding and reasoning over QA context and related commonsense knowledge,such as a structured Knowledge Graph(KG).Existing studies combine language models and graph neural networks to model ***,traditional knowledge graph are mostly concept-based,ignoring direct path evidence necessary for accurate *** this paper,we propose MRGNN(Meta-path Reasoning Graph Neural Network),a novel model that comprehensively captures sequential semantic information from concepts and *** MRGNN,meta-paths are introduced as direct inference evidence and an original graph neural network is adopted to aggregate features from both concepts and paths *** conduct sufficient experiments on the CommonsenceQA and OpenBookQA datasets,showing the effectiveness of ***,we conduct further ablation experiments and explain the reasoning behavior through the case study.

关键词： question answering knowledge graph graph neural network meta-path reasoning

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Distributed Fault Estimation for Nonlinear Systems With Sensor Saturation and Deception Attacks Using Stochastic Communication Protocols

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IEEE/CAA Journal of Automatica Sinica 2024年第8期11卷 1865-1876页

作者： Weiwei Sun Xinci Gao Lusong Ding Xiangyu Chen institute of Automation Qufu Normal UniversityQufu 273165China

This paper is aimed at the distributed fault estimation issue associated with the potential loss of actuator efficiency for a type of discrete-time nonlinear systems with sensor *** the distributed estimation structure under consideration,an estimation center is not necessary,and the estimator derives its information from itself and neighboring nodes,which fuses the state vector and the measurement *** an effort to cut down data conflicts in communication networks,the stochastic communication protocol(SCP)is employed so that the output signals from sensors can be ***,a recursive security estimator scheme is created since attackers randomly inject malicious signals into the selected *** this basis,sufficient conditions for a fault estimator with less conservatism are presented which ensure an upper bound of the estimation error covariance and the mean-square exponential boundedness of the estimating ***,a numerical example is used to show the reliability and effectiveness of the considered distributed estimation algorithm.

关键词： Actuator fault deception attacks distributed estimation sensor saturation stochastic communication protocol(SCP).

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Synthesis,chemical bonding and reactivity of new medium-sized polyarsenides

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Chinese Chemical Letters 2024年第7期35卷 497-501页

作者： Xu-Hui Yue Xiang-Wen Zhang Hui-Min He Lei Qiao Zhong-Ming Sun State Key Laboratory of Element-Organic Chemistry Tianjin Key Lab for Institution Rare Earth Materials and ApplicationsSchool of Materials Science and EngineeringNankai UniversityTianjin 300350China Department of Physics Institute of Computational and Applied PhysicsTaiyuan Normal UniversityJinzhong 030619China

Gaining an understanding of the growth mechanism from single atoms to clusters and bulk materials continues to present a ***,it is important to explore the evolving trends of clusters in the structure and properties during the size *** this work,we report the synthesis and characterization of two medium-sized chain-like polyarsenic anions.[As_(21)]^(3-)represents a trimeric example of polyarsenic anion assembled through oxidative coupling of As_(7)^(3-)*** anion As_(18)^(4-)included in[As_(18)MO_(2)(CO)_(8)]^(4-)is regarded as formed by two realgar-type As_(8)subunits connected by a dinuclear AsAs *** As_(18)cluster was previously predicted by theory,and this is the first time successfully synthesized using wet chemistry ***,small-sized polyarsenides As_(2)^(2-)and As_(10)^(2-)were found in compound[K(18-crown-6)]_(3)[As_(10)]_(0.5)[As_(4){Mo(CO)_(3)}_(2)]_(0.5)·*** these,the former exhibits coordination with metal ***-crystal X-ray diffraction combined with quantum chemical calculations revealed the formation of double bonded As_(2)^(2-)stabilized by metal carbonyl *** work demonstrates a novel synthetic approach for the preparation of new polyarsenides and highlights their intriguing bonding characteristics,laying the foundation for the synthesis of such compounds and paving the way for their potential applications.

关键词： Polyarsenide Zintl anions Chain-like cluster DFT calculations AdNDP

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