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Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Chinese Medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui zhang Shuhui Yang Kezhuo Shang Jie Li pengju zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing zhang Department of Physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China Department of Physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life Sciences Westlake UniversityHangzhouZhejiang 310024China Key Laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to chemotherapy.This study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic neoplasms.Methods:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type MEFs.Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis.The efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in vitro.Immuno-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver cancer.Results:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated cells.Boosted nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of MTX.Moreover,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.Conclusion:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver cancer.Since repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

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Evaluation of Energy Efficiency and Analysis of Influencing Factors of Company CW’s Manufacturing Workshops

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Journal of Electronic Research and Application 2024年第2期8卷 18-26页

作者： pengju zhang Business School Shandong University of TechnologyZibo 255000China

In this work,the Slacks-Based Measure(SBM)model within Data Envelopment Analysis was employed to establish a set of indicators for evaluating the energy efficiency of manufacturing workshops.The energy efficiency of 12 Company CW’s manufacturing workshops from 2016 to 2022 was assessed.The findings indicated that aside from a few workshops operating at the production frontier,the rest exhibit significant fluctuations in energy efficiency and generally low energy efficiency.Subsequently,a combined GRA-Tobit analysis model was introduced to identify factors influencing the energy efficiency of Company CW’s manufacturing workshops.Regression analysis revealed that technological investments,employee quality,workshop production scale,investment in clean energy,and the level of pollution control all significantly impact the energy efficiency of Company CW’s manufacturing workshops.By evaluating the energy efficiency of Company CW’s manufacturing workshops and studying their influencing factors,this research aids company managers in understanding the energy efficiency of the manufacturing process.It optimizes the combination of various production elements,thereby offering effective guidance for improving the energy efficiency issues of the company’s manufacturing workshops,which can contribute to enhancing the corporation’s overall energy efficiency.

关键词： Manufacturing workshop energy efficiency Energy efficiency evaluation Data Envelopment Analysis(DEA) GRA-Tobit model

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Consensus Control for Multiple Euler-Lagrange Systems Based on High-Order Disturbance Observer:An Event-Triggered Approach

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IEEE/CAA Journal of Automatica Sinica 2022年第5期9卷 945-948页

作者： Xinchen Guo Guoliang Wei Meng Yao pengju zhang Department of Control Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Business School University of Shanghai for Science and TechnologyShanghai 200093China College of Science University of Shanghai for Science and TechnologyShanghai 200093China

Dear editor,This letter addresses the leader-following consensus problem(LFCP)for multiple Euler-Lagrange(EL)systems with a directed topology.Firstly,a local high-order disturbance observer(HODO)is put forward to estimate the compound disturbance for each EL system itself,and the estimate error can ultimately achieve zero.Based on this HODO,an event-based distributed sliding mode control protocol is proposed to solve the LFCP of multiple EL systems.Furthermore,the reachability of the sliding mode surface is analyzed.Besides,it should be pointed out that the interval between any two triggering instants is a strictly positive value,hence the well-known Zeno behavior is avoided for the developed event-based protocol.Finally,the effectiveness of the proposed HODO and control protocol is further verified by a numerical simulation.

关键词： disturbance hence editor

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Insight into the Permeability and Microstructure Evolution Mechanism of the Sliding Zone Soil: A Case Study from the Huangtupo Landslide, Three Gorges Reservoir, China

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Journal of Earth Science 2024年第3期35卷 941-954页

作者： Qianyun Wang Huiming Tang pengju An Kun Fang Junrong zhang Minghao Miao Qingwen Tan Lei Huang Shengming Hu Badong National Observation and Research Station of Geohazards China University of GeosciencesWuhan 430074China Faculty of Engineering China University of GeosciencesWuhan 430074China Institute of Rock Mechanics Ningbo UniversityNingbo 315211China National and Provincial Joint Engineering Laboratory for the Hydraulic Engineering Safety and Efficient Utilization of Water Resources of Poyang Lake Basin Nanchang Institute of TechnologyNanchang 330099China

A large number of laboratory investigations related to the permeability have been conducted on the sliding zones.Yet little attention has been paid to the particular sliding zones of the slideprone Badong Formation.Here,we experimentally investigate the permeability nature and the mechanism of seepage in the viscous sliding zone of the Huangtupo Landslide.Saturated seepage tests have been performed first with consideration of six dry densities and thirteen hydraulic gradients,in conjunction with the mercury intrusion porosimetry test and scanning electron microscopy test for the microstructure analysis after seepage.The results show that seepage in the sliding zone soil does not follow Darcy’s Law,since there is a threshold hydraulic gradient(i0)below which no flow is observed and a critical hydraulic gradient(icr)over which the hydraulic conductivity(K)tends to be stable.The percentage of bound water could be responsible for the occurrence of i0 and icr.Furthermore,pore size distributions(PSD)less than 0.6µm and between 10 and 90µm exhibit positive and negative correlations with the i0,respectively,indicating that the i0 is related to the PSD.The mechanism accounting for this result is that pore water pressure forces fine clay particles into the surrounding large pores and converts arranged particles to discretely distributed ones,thereby weakening the connectivity of pores.The seepages in the sliding zones behave differently from that in the sliding mass and sliding bed in response to the permeability.

关键词： reservoir landslides sliding zone soil permeability microstructure seepage.

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Interplay between the atomic structures and superconductivity of two-monolayer Pb films

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Science China(Physics,Mechanics & Astronomy) 2024年第1期67卷 90-98页

作者： Kun Xie Ze Huang pengju Li Yumin Xia Desheng Cai Yitong Gu Yuzhou Liu Fangliang Cai Runxiao zhang Haohao Shi Ping Cui Shengyong Qin International Center for Quantum Design of Functional Materials(ICQD) University of Science and Technology of ChinaHefei 230026China CAS Key Laboratory of Strongly Coupled Quantum Matter Physics Department of PhysicsUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China

Superconductors with reduced dimensionality have been widely explored for their exotic superconducting behaviors.Especially,at the two-dimensional limit,two-monolayer Pb films with two types of structures provide an ideal platform to unveil the underlying superconducting mechanism[Science 324,1314(2009)].Here,by combining scanning tunneling microscopy(STM)with the first-principle calculations,we successfully identify that these two types have different atomic lattice structures with varying stacking phases,which further enables us to calculate the phonon spectrum and electron phonon coupling strength of each type.The theoretical calculations are in good agreement with tunneling spectroscopy measurements of the superconducting transition temperatures(T_(c)),which established a correlation between atomic structures and superconductivity.Moreover,it was observed that the higher T_(c)of these two types also possess higher out-of-plane upper critical magnetic fields(Hc2).These findings will provide important new insights into two-dimensional superconductivity at the atomic level.

关键词： 2 ML Pb films superconductivity atomic structure scanning tunneling microscopy first-principle calculations

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SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors

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Cellular & Molecular Immunology 2024年第3期21卷 213-226页

作者： Sixin Liang Rui Zheng Baile Zuo Jia Li Yiyi Wang Yujie Han Hao Dong Xiaojuan Zhao Yiting zhang pengju Wang Ruotong Meng Lintao Jia Angang Yang Bo Yan State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologyFourth Military Medical UniversityXi’anShaanxi710032China School of Medicine Technology Xinxiang Medical UniversityXinxiangHenan453003China Department of Obstetrics and Gynecology Xijing Hospital of Fourth Military Medical UniversityXi’anShaanxi710032China College of Life Science Yan’an UniversityYan’anShaanxi716000China Department of Immunology Fourth Military Medical UniversityXi’anShaanxi710032China

Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment(TME)and systemic toxicity caused by excessive cytokine release.As a key regulator of the immunosuppressive TME,TGF-βpromotes cytokine synthesis via the NF-κB pathway.Here,we coexpressed SMAD7,a suppressor of TGF-βsignaling,with a HER2-targeted CAR in engineered T cells.These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion,which enabled sustained tumoricidal capacity after continuous antigen exposure.Moreover,SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells.Mechanistically,SMAD7 downregulated TGF-βreceptor I and abrogated the interplay between the TGF-βand NF-κB pathways in CAR-T cells.As a result,these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β.SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids.Therefore,our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.

关键词： TGF-βpathway SMAD7 NF-κB pathway CAR-T-cell therapy Cytokine release syndrome(CRS)

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Robust Watermarking Algorithm for Medical Volume Data Based on Polar Cosine Transform and 3D-DCT

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Computers, Materials & Continua 2023年第6期75卷 5853-5870页

作者： pengju zhang Jingbing Li Uzair Aslam Bhatti Jing Liu Yen-wei Chen Dekai Li Lei Cao School of Information and Communication Engineering Hainan UniversityHaikou570100China State Key Laboratory of Marine Resource Utilization in the South China Sea Hainan UniversityHaikou570100China Research Center for Healthcare Data Science Zhejiang LabHangzhou311121China Graduate School of Information Science and Engineering Ritsumeikan UniversityKyoto5258577Japan

The amount of 3D data stored and transmitted in the Internet of Medical Things(IoMT)is increasing,making protecting these medical data increasingly prominent.However,there are relatively few researches on 3D data watermarking.Moreover,due to the particularity of medical data,strict data quality should be considered while protecting data security.To solve the problem,in the field of medical volume data,we proposed a robust watermarking algorithm based on Polar Cosine Transform and 3D-Discrete Cosine Transform(PCT and 3D-DCT).Each slice of the volume data was transformed by PCT to obtain feature row vector,and then the reshaped three-dimensional feature matrix was transformed by 3D-DCT.Based on the contour information of the volume data and the detail information of the inner slice,the visual feature vector was obtained by applying the per-ceptual hash.In addition,the watermark was encrypted by a multi-sensitive initial value Sine and Piecewise linear chaotic Mapping(SPM)system,and embedded as a zero watermark.The key was stored in a third party.Under the same experimental conditions,when the volume data is rotated by 80 degrees,cut 25%along the Z axis,and the JPEG compression quality is 1%,the Normalized Correlation Coefficient(NC)of the extracted watermark is 0.80,0.89,and 1.00 respectively,which are significantly higher than the comparison algorithm.

关键词： Volume data watermark zero watermark SPM PCT and 3D-DCT

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Dynamic aggregation of carbon dots self-stabilizes symmetry breaking for exceptional hydrogen production with near-infrared light

Aggregate

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Aggregate 2024年第1期5卷 385-397页

作者： Qi zhang Ya zhang Hu Shi Hongxia zhang Jianghong Zhao Zhanfeng Zheng Hengquan Yang pengju Yang School of Chemistry and Chemical Engineering Shanxi UniversityTaiyuanChina Engineering Research Center of Ministry of Education for Fine Chemicals Shanxi UniversityTaiyuanChina Institute of Molecular Science Shanxi UniversityTaiyuanChina State Key Laboratory of Coal Conversion Institute of Coal ChemistryChinese Academy of SciencesTaiyuanChina

Developing new photosystems that integrate broad-band near-infrared(NIR)light harvesting and efficient charge separation is a long-sought goal in the photocatalytic community.In this work,we develop a novel photochemical strategy to prepare light-active carbon dots(CDs)under room temperature and discover that the aggregation of CDs can broaden the light absorption to the NIR region due to the electronic couplings between neighboring CDs.Importantly,the dynamic noncovalent interactions within CD aggregates can stabilize symmetry breaking and thus induce large dipole moments for charge separation and transfer.Furthermore,the weak non-covalent interactions allow for flexible design of the aggregated degrees and the local electronic structures of CD aggregates,further strengthening NIR-light harvesting and charge separation efficiency.As a result,the CD aggregates achieve a record apparent quantum yield of 13.5%at 800 nm,which is one of the best-reported values for NIR-light-driven hydrogen photosynthesis to date.Moreover,we have prepared a series of different CDs and also observed that these CDs after aggregation all exhibit outstanding NIR-responsive photocatalytic hydrogen production activity,suggesting the universality of aggregation-enhanced photocatalysis.This discovery opens a new promising platform for using CD aggregates as efficient light absorbers for solar conversion.

关键词： aggregation charge separation hydrogen production near-infrared light photocatalysis

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整合、营造、适配——呼和浩特英华学校综合楼设计

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建筑学报 2024年第1期 71-72页

作者：张鹏举内蒙古工业大学建筑学院呼和浩特010051 内蒙古工大建筑设计有限责任公司呼和浩特010051

呼和浩特英华学校是一所小学、初中、高中一贯制的全封闭管理的私立寄宿学校,位于呼和浩特近郊。因其用地规模有限,在2021年加建综合楼(图1)时,需要在较小的用地内实现教室、图书馆、报告厅、展厅、宿舍、食堂、学生沙龙以及一定的体育... 详细信息

呼和浩特英华学校是一所小学、初中、高中一贯制的全封闭管理的私立寄宿学校,位于呼和浩特近郊。因其用地规模有限,在2021年加建综合楼(图1)时,需要在较小的用地内实现教室、图书馆、报告厅、展厅、宿舍、食堂、学生沙龙以及一定的体育活动空间等多项功能。显然,空间与功能的整合及其动线组织是设计的主线。

关键词：报告厅用地规模一所图书馆寄宿学校呼和浩特全封闭管理一贯制

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Road map for, and technical challenges of, carbon-nanotube integrated circuit technology

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National Science Review 2024年第3期11卷 14-16页

作者： Jia Si Panpan zhang Zhiyong zhang Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics School of Electronics Peking University State Key Laboratory of Information Photonics and Optical Communications Beijing University of Posts and Telecommunications

The past decade has witnessed an explosion of research on carbon-nanotube(CNT) electronics due to their outstanding properties, including an ultrathin body, a high carrier mobility and a high saturation velocity.

关键词： TRANSISTORS

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