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Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

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World Journal of Stem Cells 2024年第5期16卷 512-524页

作者： Hang Zhang Ling-zi wu Zhen-Yu Liu zi-Bing Jin Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

关键词： Cell junction Cellular differentiation Extracellular vesicle Human induced pluripotent stem cells Transcriptomics Proteomics

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High-throughput and simultaneous inertial separation of tumor cells and clusters from malignant effusions using spiral-contraction-expansion channels

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Microsystems & Nanoengineering 2024年第2期10卷 91-99页

作者： Zhixian Zhu Hui ren Dan wu Zhonghua Ni Nan Xiang School of Mechanical Engineering and Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical InstrumentsSoutheast University211189NanjingChina School of Mechanical Technology Wuxi Institute of TechnologyNo.1600 Gaolang West Road214129WuxiChina Department of Oncology Jiangyin People’s Hospital214400JiangyinChina

Tumor cell clusters are regarded as critical factors in cancer pathophysiology,and increasing evidence of their higher treatment resistance and metastasis compared to single tumor cells has been obtained.However,existing cell separation methods that are designed for single tumor cells cannot be used to simultaneously purify tumor cell clusters.To address this problem,we demonstrated a microfluidic approach for the high-throughput,continuous-flow ternary separation of single tumor cells,tumor cell clusters,and WBCs from clinical pleural or abdominal effusions by coupling slanted spiral channels and periodic contraction-expansion arrays.We first systematically explored the influence of particle size and flow rate on particle focusing.The separation performance indicated that 94.0%of WBCs were removed and more than 97%of MDA-MB-231 tumor cells were recovered at a high flow rate of 3500µL/min.Moreover,more than 90%of tumor cell clusters were effectively preserved after separation.Finally,we successfully applied our device for the ternary separation of single tumor cells,tumor cell clusters,and WBCs from different malignant effusions collected from patients with metastatic cancer.Thus,our spiral-contraction-expansion device has potential as a sample pretreatment tool for the cytological diagnosis of malignant effusions.

关键词： separation contraction removed

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Microstructure and mechanical properties of a cast TRIP-assisted multiphase stainless steel

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China Foundry 2024年第3期21卷 221-228页

作者： Meng-xin Wang zi-xiang wu Jing-yu He Xiang Chen School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Ministry of EducationBeijing 100084China

Stainless steels are used in a wide range of complex environments due to their excellent corrosion resistance.Multiphase stainless steels can offer an excellent combination of strength,toughness and corrosion resistance due to the coexistence of different microstructures.The microstructure and mechanical properties of a novel cast multiphase stainless steel,composed of martensite,ferrite,and austenite,were investigated following appropriate heat treatment processes:solution treatment at 1,050℃ for 0.5 h followed by water quenching to room temperature,and aging treatment at 500℃ for 4 h followed by water quenching to room temperature.Results show reversed austenite is formed by diffusion of Ni element during aging process,and the enrichment of Ni atoms directly determines the mechanical stability of austenite.The austenite with a lower Ni content undergoes a martensitic transformation during plastic deformation.The tensile strength of the specimen exceeds 1,100 MPa and the elongation exceeds 24%after solid solution,and further increases to 1,247 MPa and 25%after aging treatment.This enhancement is due to the TRIP effect of austenite and the precipitation of the nanoscale G-phase pinning dislocations in ferrite and martensite.

关键词： multiphase stainless steel mechanical properties TRIP effect reversed austenite G-phase

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Precise phase adjustment and antibacterial property of copper sulfide particles in confined mesoporous silica nanoreactor

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Particuology 2024年第2期85卷 113-121页

作者： Shiyu Xu Jinyong wu Zhongzhen ren Dechao Niu Low Dimensional Materials Chemistry Laboratory Key Laboratory for Ultrafine Materials of Ministry of EducationFrontier Science Center of the Materials Biology and Dynamic ChemistryShanghai Engineering Research Center of Hierarchical NanomaterialsSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China

Bacteria-caused wound infection greatly threatens human health,thus developing an efficient and safe antibacterial agent without drug resistance is still a great challenge.Herein,a confined vulcanization strategy is proposed to construct copper sulfides-loaded dual-mesoporous silica nanospheres(Cux-Sy@DMSNs)with various crystal phases for reactive oxygen species(ROS)-mediated and photothermal antibacterial application.With the pore confinement of DMSNs,the crystal phases of copper sulfides including CuS,Cu_(9)S_(5)and Cui.96S can be easily controlled by changing the vulcanization temperature.The relationships between the crystal phases and photothermal properties as well as peroxidase-like activity of copper sulfides were systematically investigated.Results show that the obtained CuS@DMSNs exhibited higher photothermal ability with remarkable photothermal conversion efficiency of 36.86%in the second near-infrared region(NIR-II)and better peroxidase-like activity,compared to those of Cu_(9)S_(5)@DMSNs and Cu_(1.96)S@DMSNs.As a result,the in vitro experiments showed the good antibacterial effect against both gram-negative E.coli and gram-positive S.aureus under 1064 nm laser irradiation and the presence of H_(2)O_(2).Besides,the CCK-8 assay indicated that CuS@p-DMSNs have minimal cytotoxicity against normal human umbilical vein endothelial cells at the ranged concentrations.Therefore,the resultant CuS@p-DMSNs could act as a promising antibacterial agent for deep wound bacterial infection treatment.

关键词： Copper sulfides Mesoporous silica Photothermal Reactive oxygen species Antibacterial agent

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An interlaminar damage shell model for typical composite structures

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Chinese Journal of Aeronautics 2024年第1期37卷 118-137页

作者： Jie ZHOU Zhen wu Zhengliang LIU Xiaohui ren School of Aeronautics Northwestern Polytechnical UniversityXi’an 710072China National Key Laboratory of Strength and Structural Integrity Xi’an 710065China School of Mechanical Engineering Xi’an Aeronautical UniversityXi’an 710065China

Using the plate/shell elements in commercial software,accurate analysis of interlaminar initial damage in typical composite structures is still a challenging issue.To propose an accurate and efficient model for analysis of interlaminar initial damage,the following work is carried out:(A)A higher-order theory is firstly proposed by introducing the local Legendre polynomials,and then a novel shell element containing initial damage prediction is developed,which can directly predict transverse shear stresses without any postprocessing methods.Unknown variables at each node are independent of number of layers,so the proposed model is more efficient than the 3D-FEM.(B)Compression experiment is carried out to verify the capability of the proposed model.The results obtained from the proposed model are in good agreement with experimental data.(C)Several examples have been analyzed to further assess the capability of the proposed model by comparing to the 3D-FEM results.Moreover,accuracy and efficiency have been evaluated in different damage criterion by comparing with the selected models.The numerical results show that the proposed model can well predict the initial interlaminar damage as well as other damage.Finally,the model is implemented with UEL subroutine,so that the present approach can be readily utilized to analyze the initial damage in typical composite structures.

关键词： Compression experiment Finite element method Initial damage Interlaminar stress Plate/shell element

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The Sequential Pricing of Ride-Hailing System with rental Service in the Context of Fleet Electrification

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Journal of Systems Science and Systems Engineering 2024年第1期33卷 77-105页

作者： Yaoyao Ku Peng wu Qiang ren Yiqing Wang Business School Sichuan UniversityChengdu610065China

Surging demand and reduced capacity in the ride-hailing industry have prompted numerous ride-hailing platforms to build their own car-rental services catering to drivers who do not possess private vehicles. However, the trade-off between the ride-hailing service and the car-rental service is an important issue that is still unclear in theory. Moreover, ride-hailing platforms are transitioning towards all-electric fleets in the context of Carbon Neutrality goals and government regulations. This paper considers a ride-hailing system comprising a monopolist ride-hailing platform, an electric vehicle (EV) rental firm, and a gasoline vehicle (GV) rental firm. Furthermore, we build a stylized model to study the sequential pricing of the system. The equilibrium outcomes show the significant impact of the ride-hailing platform’s decision to continue or withdraw offering EV rental services on EV and GV drivers’ net earnings, rental prices, and wages. The ride-hailing platform providing EV rental services increases EV drivers’ net earnings but decreases the GV driver wages and rental prices. However, the EV rental service offered by the ride-hailing platform does not necessarily lead to an increased total profit for the system. The improved profitability of the system by the ride-hailing platform providing EV rental services is contingent upon lower rider prices and higher fuel costs. The ride-hailing platform’s EV rental services provision also effectively fosters the ride-hailing fleet’s electrification. Furthermore, as the number of riders increases, the ride-hailing platform should reduce the commission rate for EV drivers to maintain competitiveness and profitability.

关键词： Ride-hailing system car rental fleet electrification sequential pricing differential wage scheme

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Fault diagnosis of HVAC system with imbalanced data using multi-scale convolution composite neural network

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Building Simulation 2024年第3期17卷 371-386页

作者： Rouhui wu Yizhu ren Mengying Tan Lei Nie School of Mechanical Engineering Hubei University of TechnologyWuhan430068China Industrial Research Institute of Xiangyang Hubei University of Technology Xiangyang441100China

Accurate fault diagnosis of heating,ventilation,and air conditioning(HVAC)systems is of significant importance for maintaining normal operation,reducing energy consumption,and minimizing maintenance costs.However,in practical applications,it is challenging to obtain sufficient fault data for HVAC systems,leading to imbalanced data,where the number of fault samples is much smaller than that of normal samples.Moreover,most existing HVAC system fault diagnosis methods heavily rely on balanced training sets to achieve high fault diagnosis accuracy.Therefore,to address this issue,a composite neural network fault diagnosis model is proposed,which combines SMOTETomek,multi-scale one-dimensional convolutional neural networks(M1DCNN),and support vector machine(SVM).This method first utilizes SMOTETomek to augment the minority class samples in the imbalanced dataset,achieving a balanced number of faulty and normal data.Then,it employs the M1DCNN model to extract feature information from the augmented dataset.Finally,it replaces the original Softmax classifier with an SVM classifier for classification,thus enhancing the fault diagnosis accuracy.Using the SMOTETomek-M1DCNN-SVM method,we conducted fault diagnosis validation on both the ASHRAE RP-1043 dataset and experimental dataset with an imbalance ratio of 1:10.The results demonstrate the superiority of this approach,providing a novel and promising solution for intelligent building management,with accuracy and F1 scores of 98.45%and 100%for the RP-1043 dataset and experimental dataset,respectively.

关键词： fault diagnosis chiller imbalanced data SMOTETomek multi-scale neural networks

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Nonreciprocal generation of Schrodinger cat state induced by topology

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Science China(Physics,Mechanics & Astronomy) 2024年第4期67卷 23-30页

作者： zi-Hao Li Li-Li Zheng Ying wu Xin-You Lü School of Physics and Institute for Quantum Science and Engineering Huazhong University of Science and Technologyand Wuhan Institute of Quantum TechnologyWuhan 430074China Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education Jianghan UniversityWuhan 430074China

The Schrodinger cat state produced differently in two directions is anticipated to be a critical quantum resource in quantum information technologies.By exploring the interplay between quantum nonreciprocity and topology in a one-dimensional microcavity array,we obtain the Schrodinger cat state(a pure quantum state)in a chosen direction at the edge cavity,whereas a classical state in the other direction.This nonreciprocal generation of the cat state originates from the topologically protected chiralitymode excitation in the nontrivial phase,but in the trivial phase,the nonreciprocal generation of cat state vanishes.Thus,our proposal is switchable by tuning the parameters so that a topological phase transition occurs.Moreover,the obtained cat state has nonreciprocal high fidelity,nonclassicality,and quantum coherence,which are sufficient to be used in various one-way quantum technologies,e.g.,invisible quantum sensing,noise-tolerant quantum computing,and chiral quantum networks.Our work provides a general approach to control quantum nonreciprocities with the topological effect,which substantially broadens the fields of nonreciprocal photonics and topological physics.

关键词： Schr?dinger cat state nonreciprocity topology

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Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C.elegans

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang zi Wang zixing wu Di Chen Model Animal Research Center of Medical School Nanjing UniversityNanjingJiangsu 210061China Zhejiang University-University of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China Department of Colorectal Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

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Chain Dynamics Heterogeneity in Plasticized Poly(vinyl butyral)(PVB) as Elucidated by Solid-State NMR

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Chinese Journal of Polymer Science 2024年第1期42卷 113-124,I0010页

作者： Jing Lv Xu Chen zi-Shuo wu Ya-Hui Li Wei Chen National Synchrotron Radiation Laboratory Anhui Provincial Engineering Laboratory of Advanced Functional Polymer FilmCAS Key Laboratory of Soft Matter ChemistryUniversity of Scienceand Technology of ChinaHefei 230026China

The chain dynamics heterogeneity of the poly(vinyl butyral)(PVB) plasticized by triethylene glycol bis(2-ethylhexa noate)(TEG-EH) was investigated by various solid-state NMR techniques.The plasticized PVB shows two domains in distinct molecular dynamics differences,namely,rigid and soft domains,where the latter is the plasticizer-rich domain.The time domain low field NMR was first used to investigate the dynamics heterogeneity of the plasticized PVB,and the results show the decreasing activated energy of components in the soft domain of plasticized PVB(E_a=20.2 kJ/mol) as compared with that of the pristine one(E_a=24.3 kJ/mol).Detailed dynamics heterogeneity was obtained by high-field NMR with site-specific features.The quadrupole-echo ~2H-NMR was adopted to elucidate the dynamics heterogeneity of the vinyl alcohol(VA) units,where only the hydroxyl group of VA is deuterated.The ~1H-^(13)C WISE NMR spectra show that there is not much difference in the mobility of the VB unit in PVB with and without plasticizer,whereas the glass transition temperature differed by approximately 53℃.This is further supported by Torchia's T_1 relaxation measurements.The origin of such an unusual phenomenon is attributed to the critical role of the remaining VA(~22%) in the soft domain,where the VA units locally aggregate through hydrogen bonding.Also,the existence of a mobility gradient in the VB unit has been demonstrated.Moreover,the mobility difference for VB with different stereo-geometry(meso or racemic conformation) is observed for the first time.This indicates the importance of modulating the ratio of meso over racemic VB for controlling the macroscopic perfo rmance of PVB.

关键词： Poly(vinyl butyral) Dynamics heterogeneity Plasticizer Solid state NMR

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