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Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish(Danio rerio)

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Zoological Research 2024年第3期45卷 567-574页

作者： Peng-cheng Wang Hao Deng Rang Xu jiu-Lin Du Rongkun Tao Department of Pediatric Cardiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Medical School Kunming University of Science and TechnologyKunmingYunnan 650500China Scientific Research Center Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China University of Chinese Academy of Sciences Beijing 100049China School of Life Science and Technology ShanghaiTech UniversityShanghai 200031China

Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes.However,their activity markedly diminishes with payloads exceeding 11 kb.Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs,improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics,metabolic engineering,and transgenic animal production.In this study,we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer(QBI SP163,ST)and enhanced the nuclear targeting ability using the nuclear localization protein H2B(SHT).The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures(H1299),comparable to the well-established super PiggyBac system.Furthermore,mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads(8 kb,14 kb,and 24 kb)into zebrafish(Danio rerio).This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.

关键词： Zebrafish Tol2 transposase Transgene Large payload Synthetic biology

Compliance motion control of the hydraulic dual-arm manipulator with adaptive mass estimation of unknown object

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Frontiers of Mechanical Engineering 2024年第1期19卷 35-52页

作者： Bolin SUN Min cheng Ruqi DING bing XU State Key Laboratory of Mechanical Transmissions Chongqing UniversityChongqing 400044China Key Laboratory of Conveyance and Equipment(Ministry of Education) East China Jiaotong UniversityNanchang 330013China State Key Laboratory of Fluid Power and Mechatronic Systems Zhejiang UniversityHangzhou 310027China

Given the limited operating ability of a single robotic arm,dual-arm collaborative operations have become increasingly prominent.Compared with the electrically driven dual-arm manipulator,due to the unknown heavy load,difficulty in measuring contact forces,and control complexity during the closed-chain object transportation task,the hydraulic dual-arm manipulator(HDM)faces more difficulty in accurately tracking the desired motion trajectory,which may cause object deformation or even breakage.To overcome this problem,a compliance motion control method is proposed in this paper for the HDM.The mass parameter of the unknown object is obtained by using an adaptive method based on velocity error.Due to the difficulty in obtaining the actual internal force of the object,the pressure signal from the pressure sensor of the hydraulic system is used to estimate the contact force at the end-effector(EE)of two hydraulic manipulators(HMs).Further,the estimated contact force is used to calculate the actual internal force on the object.Then,a compliance motion controller is designed for HDM closed-chain collaboration.The position and internal force errors of the object are reduced by the feedback of the position,velocity,and internal force errors of the object to achieve the effect of the compliance motion of the HDM,i.e.,to reduce the motion error and internal force of the object.The required velocity and force at the EE of the two HMs,including the position and internal force errors of the object,are inputted into separate position controllers.In addition,the position controllers of the two individual HMs are designed to enable precise motion control by using the virtual decomposition control method.Finally,comparative experiments are carried out on a hydraulic dual-arm test bench.The proposed method is validated by the experimental results,which demonstrate improved object position accuracy and reduced internal force.

关键词： hydraulic dual-arm manipulator compliance motion control unknown object adaptive mass estimation nonlinear control

Evaluating combined bevacizumab and XELOX in advanced colorectal cancer: Serum markers carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 analysis

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World Journal of Clinical Cases 2024年第1期12卷 15-23页

作者： Dong-bing Zhou Jun cheng Xiong-Hui Zhang Department of Gastroenterology The Second People's Hospital of Jingzhou HubeiJingzhou 434000Hubei ProvinceChina Department of Gastrointestinal Surgery Qianjiang Central HospitalQianjing 433100Hubei ProvinceChina Department of Gastroenterology Xiantao First People's Hosepital Affiliated to Yangtze UniversityXiantao 433000Hubei ProvinceChina

BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)and oxaliplatin.Serum tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125 and CA199 are prognostic factors for various tumors.AIM To investigate evaluating combined bevacizumab(BEV)and XELOX in advanced colorectal cancer:Serum markers CEA,CA125,CA199 analysis.METHODS In this retrospective study,a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received.The control group was treated with XELOX plus CAP(n=47),while the observation group was treated with XELOX plus CAP and BEV(n=47).Several indexes were assessed in both groups,including disease control rate(DCR),incidence of adverse effects,serum marker levels(CEA,CA125,and CA19)and progression-free survival(PFS).RESULTS After 9 wk of treatment,the serum levels of CEA,CA199 and CA125 in the observation group were significantly lower than those in the control group(P0.05).CONCLUSION On the basis of XELOX treatment,the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.

关键词： Metastatic colorectal cancer Bevacizumab Capecitabine XELOX Tumor markers

Differential Operator Approach to■quantum Groups and Their Oscillator Representations

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Acta Mathematica Sinica,English Series 2024年第5期40卷 1360-1374页

作者： Zhao bing FAN Ji cheng GENG Shao Long HAN College of Mathematical Science Harbin Engineering UniversityHarbin 150001P.R.China

For a quasi-split Satake diagram,we define a modified q-Weyl algebra,and show that there is an algebra homomorphism between it and the corresponding■quantum group.In other words,we provide a differential operator approach to■quantum groups.Meanwhile,the oscillator representations of■quantum groups are obtained.The crystal basis of the irreducible subrepresentations of these oscillator representations are constructed.

关键词： ■quantum group differential operator oscillator representation crystal basis

Strategies that regulate LSD1 for novel therapeutics

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai bing cheng Shaotong Li Enhui Guo Junwei Fu Ting Ma Bin Yu School of Pharmaceutical Sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various diseases.LSD1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic target.Several LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical stage.LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or activation.While the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other factors.For example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1.Moreover,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase activity.Therefore,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

Microstructural characterization and mechanical properties of(TiC+TiB)/TA15 composites prepared by an in-situ synthesis method

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China Foundry 2024年第2期21卷 168-174页

作者： Zhi-yong Zhang Jiao-jiao cheng Jia-qi Xie Shi-bing Liu Kun Shi Jun Zhao Shenyang Research Institute of Foundry Co. Ltd.CAMShenyang 110022China National Key Laboratory of Advanced Casting Technologies Shenyang 110022China

Titanium matrix composites reinforced with ceramic particles are considered a promising engineering material due to their combination of high specific strength,low density,and high modulus.In this study,the TA15-based composites reinforced with a volume fraction of 10% to 25%(TiB+TiC)were prepared using powder metallurgy and casting technique.Microstructural characterization and phase constitution were examined using optical microscopy(OM),scanning electron microscopy(SEM),and X-ray diffraction(XRD).In addition,the microhardness,room temperature(RT)and high temperature(HT)tensile properties of the composites were evaluated.Results revealed that the reinforcements are distributed uniformly even in the composites with a high volume of TiB and TiC.However,as the volume fraction exceeds 15%,TiB and TiC particles become coarsening and exhibit rod-like and dendritic-like morphology.Microhardness increases gradually from 321.2 HV for the base alloy to a maximum of 473.3 HV as the reinforcement increases to 25vol.%.Tensile test results indicate that a reinforcement volume fraction above 20% is beneficial for enhancing tensile strength and yield strength at high temperatures,but it has an adverse effect on room temperature elongation.Conversely,if the reinforcement volume fraction is below 20%,it can improve high-temperature elongation when the temperature exceeds 600℃.

关键词： titanium matrix composites microstucture microhardness tensile properties in-situ synthesis

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

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Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin Zhang Shuo Geng Yuxi cheng Huize Han Zhipu Fan Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

Online preparation of high-quality BN coatings with atomic diffusion based on carbon-free water-soluble precursor

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Journal of Advanced Ceramics 2024年第3期13卷 272-281页

作者： Yiang Du bing Wang Yunbo Zhang Quzhi Song Fuwen Wang cheng Han Xiaoshan Zhang Yingde Wang Science and Technology on Advanced Ceramic Fibers and Composites Laboratory College of Aerospace Science and EngineeringNational University of Defense TechnologyChangsha 410073China

Efficient and environmentally friendly production of high-quality continuous fiber coatings using current preparation methods is highly challenging due to issues such as scale and batch processing restrictions,low deposition rate,high energy consumption,and utilization of multiple environmentally hazardous steps.To address these challenges,we propose a stable and efficient wet chemical deposition coating method for high-throughput online continuous preparation of boron nitride(BN)coatings on ceramic fibers under an ambient environment.Our process involves surface modification,in-situ wet chemical deposition,and heat treatment,and all seamlessly connecting with the ceramic fiber preparation process through continuous stretching.Hydrophilic groups were introduced via surface modification enhancing wettability of the fiber surface with impregnating solution.An in-situ reaction and atom migration improve uniformity and binding of the coating.As a result,outstanding impregnation and adhesion properties are achieved.A comprehensive analysis to evaluate the impact of the BN coatings was conducted,which demonstrates that the BN-coated fibers exhibit a remarkable 36%increase in tensile strength,a 133%increase in fracture toughness,and enhanced temperature resistance of up to 1600℃.It provides a secure and efficient platform for cost-effective production of functional and high-quality coatings through targeted surface modification and rapid stretching impregnation.

关键词： polymer-derived ceramics SiC fibers wet chemical deposition atomic diffusion boron nitride(BN)coatings

A Hybrid Approach for Predicting the Remaining Useful Life of Bearings Based on the RReliefF Algorithm and Extreme Learning Machine

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1405-1427页

作者： Sen-Hui Wang Xi Kang cheng Wang Tian-bing Ma Xiang He Ke Yang School of Mechatronics Engineering Anhui University of Science and TechnologyHuainan232001China Institute of Energy Hefei Comprehensive National Science CenterHefei230031China

Accurately predicting the remaining useful life(RUL)of bearings in mining rotating equipment is vital for mining enterprises.This research aims to distinguish the features associated with the RUL of bearings and propose a prediction model based on these selected features.This study proposes a hybrid predictive model to assess the RUL of rolling element bearings.The proposed model begins with the pre-processing of bearing vibration signals to reconstruct sixty time-domain features.The hybrid model selects relevant features from the sixty time-domain features of the vibration signal by adopting the RReliefF feature selection algorithm.Subsequently,the extreme learning machine(ELM)approach is applied to develop a predictive model of RUL based on the optimal features.The model is trained by optimizing its parameters via the grid search approach.The training datasets are adjusted to make them most suitable for the regression model using the cross-validation method.The proposed hybrid model is analyzed and validated using the vibration data taken from the public XJTU-SY rolling element-bearing database.The comparison is constructed with other traditional models.The experimental test results demonstrated that the proposed approach can predict the RUL of bearings with a reliable degree of accuracy.

关键词： Bearing degradation remaining useful life estimation RReliefF feature selection extreme learning machine