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AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy

Chinese Medical Journal 2024年第2期137卷 222-231页

作者： Yichun Yin Jian Wang Junxuan Yi Kaiyue Zhang Zimeng Yin shunzi jin Baisong Zheng Public Health of College Jilin UniversityJilinChangchun 130021China Institute of Virology and AIDS Research The First Hospital of Jilin UniversityJilinChangchun 130021China NHC Key Laboratory of Radiobiology(Jilin University) JilinChangchun 130021China

Background:Radiation(IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment(TME).Wee1,a cell cycle regulator,can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1(CDK1).Meanwhile,programed death-1/programed death ligand-1(PD-1/PDL-1)blockade is closely related to TME.This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody(anti-PD-1 Ab)on radiosensitization of hepatoma.Methods:The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide(MTT)assay on human and mouse hepatoma cells HepG2,Hepa1-6,and H22.The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro.A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice,which were divided into control group,IR group,AZD1775 group,IR+AZD1775 group,IR+anti-PD-1 Ab group,and the IR+AZD1775+anti-PD-1 Ab group.Cytotoxic CD8^(+)T cells in TME were analyzed by flow cytometry.Results:Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro.AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage.AZD1775 treatment also reduced the proportion of PD-1^(+)/CD8^(+)T cells in the spleen of hepatoma subcutaneous xenograft mice.Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferonγ(IFNγ)^(+)or Ki67^(+)CD8 T cells and decreasing the levels of CD8^(+)Tregs cells in the tumor and spleen of the hepatoma mice model,indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγexpression,enhancing CD8^(+)T cells proliferation,and weakening CD8^(+)T cells depletion.Conclusions:This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improv

关键词： Hepatoma Radiation AZD1775 Anti-PD-1 antibody DNA damage Tumor microenvironment

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Combined Treatment with Bojungikgi-tang(Buzhong Yiqi Decoction) and Riluzole Attenuates Cell Death in TDP-43-Expressing Cells

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Chinese Journal of Integrative Medicine 2024年第7期30卷 616-622页

作者： Eun jin Yang Department of KM Science Research Korea Institute of Oriental Medicine

Objective: To examine the effect of combined treatment with Bojungikgi-tang(BJIGT, Buzhong Yiqi Decoction) and riluzole(RZ) in transactive response DNA-binding protein 43(TDP-43) stress granule(SG) cells, a amyotrophic lateral sclerosis(ALS) cell line using transcriptomic and molecular techniques. Methods: TDP-43 SG cells were pretreated with BJIGT(100 μg/mL), RZ(50 μmol/L), and combined BJIGT(100 μg/mL)/RZ(50 μmol/L) for 6 h before treatment with lipopolysaccharide(LPS, 200 μmol/L). Cell viability assay was performed to elucidate cell toxicity in TDP-43 SC cells using a cell-counting kit-8(CCK8) assay kit. The expression levels of cell death-related proteins, including Bax, caspase 1, cleaved caspase 3 and DJ1 in TDP-43 SG cells were examined by Western blot analysis. The autophagy-related proteins, including pmTOR/mTOR, LC3b, P62, ATG7 and Bcl-2-associated athanogene 3(Bag3) were investigated using immunofluorescence and immunoblotting assays. Results: Cell viability assay and Western blot analysis showed that combined treatment with BJIGT and RZ suppressed LPS-induced cell death and expression of cell death-related proteins, including Bax, caspase 1, and DJ1(P<0.05 or P<0.01). Immunofluorescence and immunoblotting assays showed that combined treatment with BJIGT and RZ reduced LPS-induced formation of TDP-43 aggregates and regulated autophagy-related protein levels, including p62, light chain 3b, Bag3, and ATG7, in TDP-43-expressing cells(P<0.05 or P<0.01). Conclusion: The combined treatment of BJIGT and RZ might reduce inflammation and regulate autophagy dysfunction in TDP-43-induced ALS.

关键词： Bojungikgi-tang Buzhong Yiqi Decoction transactive response DNA-binding protein 43 autophagy oxidative stress amyotrophic lateral sclerosis

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A self-centering and stiffness-controlled MEMS accelerometer

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Microsystems & Nanoengineering 2024年第1期10卷 27-40页

作者： Yiming jin Zhipeng Ma Ziyi Ye Mingkang Li Xudong Zheng Zhonghe jin School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310013China Key Laboratory of Micro/Nano-Satellite Research of Zhejiang Province Hangzhou 310007PR China

This paper presents a high-performance MEMS accelerometer with a DC/AC electrostatic stiffness tuning capability based on double-sided parallel plates(DSPPs).DC and AC electrostatic tuning enable the adjustment of the effective stiffness and the calibration of the geometric offset of the proof mass,respectively.A dynamical model of the proposed accelerometer was developed considering both DC/AC electrostatic tuning and the temperature effect.Based on the dynamical model,a self-centering closed loop is proposed for pulling the reference position of the forceto-rebalance(FTR)to the geometric center of DSPP.The self-centering accelerometer operates at the optimal reference position by eliminating the temperature drift of the readout circuit and nulling the net electrostatic tuning forces.The stiffness closed-loop is also incorporated to prevent the pull-in instability of the tuned low-stiffness accelerometer under a dramatic temperature variation.Real-time adjustments of the reference position and the DC tuning voltage are utilized to compensate for the residue temperature drift of the proposed accelerometer.As a result,a novel controlling approach composed of a self-centering closed loop,stiffness-closed loop,and temperature drift compensation is achieved for the accelerometer,realizing a temperature drift coefficient(TDC)of approximately 7μg/℃ and an Allan bias instability of less than 1μg.

关键词： stiffness electrostatic centering

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Shor's algorithm does not factor large integers in the presence of noise

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Science China(Information Sciences) 2024年第7期67卷 305-320页

作者： jin-Yi CAI College of Letters and Science University of Wisconsin

We consider Shor's quantum factoring algorithm in the setting of noisy quantum gates. Under a generic model of random noise for(controlled) rotation gates, we prove that the algorithm does not factor integers of the form pq when the noise exceeds a vanishingly small level in terms of n—the number of bits of the integer to be factored, where p and q are from a well-defined set of primes of positive density. We further prove that with probability 1-o(1) over random prime pairs(p, q), Shor's factoring algorithm does not factor numbers of the form pq, with the same level of random noise present.

关键词： random noise Shor's algorithm rotation gates quantum computing prime factorization

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Mobility of rhenium and selenium during chemical weathering and their implication for petrogenic organic carbon oxidation

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Science China Earth Sciences 2024年第3期67卷 740-750页

作者： Yuhong ZHANG jin WANG Yuanxin QU Chao ZHU Zhangdong jin State Key Laboratory of Loess and Quaternary Geology Institute of Earth EnvironmentChinese Academy of SciencesXi'an 710061China University of Chinese Academy of Sciences Beijing 100049China Xi'an Institute for Innovative Earth Environment Research Xi'an 710061China Institute of Global Environmental Change Xi'an Jiaotong UniversityXi'an 710049China

The oxidative weathering of petrogenic organic carbon(OC_(petro)) is an important source of carbon dioxide(CO_(2)) into the atmosphere on geological timescales and significantly influences the carbon cycle and global climate change. However, at present, a robust proxy to assess OC_(petro)oxidation is lacking. Riverine rhenium(Re) has emerged as a potential proxy to trace OC_(petro)oxidation, but little is known about Re sources and its relationship with OC_(petro)oxidation. To better understand the robustness of this proxy, we analyzed a shale weathering profile from the early Cambrian Shuijingtuo Formation in Chengkou County, Chongqing City, to address the mobility of Re and selenium(Se) and their relationship with the oxidation of OC_(petro)by analyses of the elemental variation and sequential extraction. The results showed that the chemical index of alteration(CIA)increases from the fresh bedrock to the weathered sections, indicating enhanced weathering intensity. Based on the sequential extraction and mass transfer coefficients(τ), Re and Se mainly exist in the organic phase of shale and are paired lost with OC_(petro) during weathering, with no obvious correlation with sulfide minerals. Furthermore, the different proportions of Re and Se loss with OC_(petro) loss can be attributed to their different geochemical behaviors during weathering. Our study supports Re as a robust proxy to trace OC_(petro) oxidation, whereas Se is the potential one. In the future, combined studies on various sedimentary rock profiles with catchment basins are needed to determine the sources of riverine Re and Se and their relationships with OC_(petro) oxidation.

关键词： Rhenium and selenium Shale Mobility OC_(petro) Chemical weathering

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Spin-based magnetic random-access memory for high-performance computing

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National Science Review 2024年第3期11卷 20-23页

作者： Kaiming Cai Tianli jin Wen Siang Lew School of Physics Huazhong University of Science and Technology Interuniversity Microelectronics Centre(IMEC) School of Physical and Mathematical Sciences Nanyang Technological University

Memory serves as a critical component in today's electronic systems for data storage and processing. In traditional computer architectures, the logic and memory units are physically separated, due to the performance gap in operational speed and capacity among memories, resulting in the fundamental limitation of the von Neumann computers.

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Mechanisms of liver injuries caused by traditional Chinese medicines

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 310-312页

作者： Shui-Fang jin Qi Pan jin-Peng Zhou Xiao-Ping Pan Intensive Care Unit The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou 310006China Institute of Liver Diseases College of Basic Medical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China The Second Clinical Medical College of Zhejiang Chinese Medical University Hangzhou 310056China

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

关键词： drugs tuberculosis TCM

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Bi-Frobenius Algebra Structures on Quantum Complete Intersections

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Acta Mathematica Sinica,English Series 2024年第6期40卷 1481-1504页

作者： Hai jin Pu ZHANG School of Mathematical Sciences Shanghai Jiao Tong UniversityShanghai 200240P.R.China

This paper is to look for bi-Frobenius algebra structures on quantum complete intersections over field k.We find a class of comultiplications,such that if√−1∈k,then a quantum complete intersection becomes a bi-Frobenius algebra with comultiplication of this form if and only if all the parameters qij=±1.Also,it is proved that if√−1∈k then a quantum exterior algebra in two variables admits a bi-Frobenius algebra structure if and only if the parameter q=±√1.While if−1/∈k,then the exterior algebra with two variables admits no bi-Frobenius algebra structures.We prove that the quantum complete intersections admit a bialgebra structure if and only if it admits a Hopf algebra structure,if and only if it is commutative,the characteristic of k is a prime p,and every ai a power of p.This also provides a large class of examples of bi-Frobenius algebras which are not bialgebras(and hence not Hopf algebras).In commutative case,other two comultiplications on complete intersection rings are given,such that they admit non-isomorphic bi-Frobenius algebra structures.

关键词： Bi-Frobenius algebras coalgebras bialgebras Hopf algebras quantum complete intersections quantum exterior algebras

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Innovation and Firm Co-ownership Network in China’s Electric Vehicle Industry

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Chinese Geographical Science 2024年第2期34卷 195-209页

作者： jin Zerun ZHU Shengjun College of Urban and Environmental Sciences Peking UniversityBeijing 100871China Laboratory for Earth Surface Pro-cesses of the Ministry of Education Peking UniversityBeijing 100871China

Firms are embedded in complex networks,where diverse ideas combine and generate new ideas.Shareholders of firms are of-ten seen as critical external resources that have significant influence on firm innovation.The current literature tends to focus on the rela-tionship between firms and their shareholders,while paying less attention to the connections between firms with the same shareholders.This article identifies two types of network spillover effects,intra-city network effect and inter-city network effect,by visualizing the co-ownership networks in China’s electric vehicle(EV)industry.We find that firms with the same shareholders,which are defined as co-owned EV firms,are more innovative than non-co-owned ones.Furthermore,there are two dominant types of firm co-ownership ties formed by corporate and financial institution shareholders.While corporate shareholders help exploiting local tacit knowledge,financial institutions are more active in bridging inter-city connections.The conclusion is confirmed at both firm and city levels.This paper theor-izes the firm co-ownership network as a new form of institutional proximity and tested the result empirically.For policy consideration,we have emphasized the importance of building formal or informal inter-firm network,and the government should further enhance the knowledge flow channel by institutional construction.

关键词： firm co-ownership intra-city network inter-city network technological innovation electric vehicle China

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Suitable region of dynamic optimal interpolation for efficiently altimetry sea surface height mapping

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Geodesy and Geodynamics 2024年第2期15卷 142-149页

作者： Jiasheng Shi Taoyong jin School of Geodesy and Geomatics Hubei Luojia LaboratoryWuhan UniversityWuhan 430079China MOE Key Laboratory of Geospace Environment and Geodesy Wuhan UniversityWuhan 430079China

The dynamic optimal interpolation(DOI)method is a technique based on quasi-geostrophic dynamics for merging multi-satellite altimeter along-track observations to generate gridded absolute dynamic topography(ADT).Compared with the linear optimal interpolation(LOI)method,the DOI method can improve the accuracy of gridded ADT locally but with low computational efficiency.Consequently,considering both computational efficiency and accuracy,the DOI method is more suitable to be used only for regional applications.In this study,we propose to evaluate the suitable region for applying the DOI method based on the correlation between the absolute value of the Jacobian operator of the geostrophic stream function and the improvement achieved by the DOI method.After verifying the LOI and DOI methods,the suitable region was investigated in three typical areas:the Gulf Stream(25°N-50°N,55°W-80°W),the Japanese Kuroshio(25°N-45°N,135°E-155°E),and the South China Sea(5°N-25°N,100°E-125°E).We propose to use the DOI method only in regions outside the equatorial region and where the absolute value of the Jacobian operator of the geostrophic stream function is higher than1×10^(-11).

关键词： Dynamic optimal interpolation Linearoptimal interpolation Satellite altimetry Sea surface height Suitable region

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