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Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C

Journal of Pharmaceutical Analysis 2023年第6期13卷 616-624页

作者： Ping Zhu Shi-You Li Jin Ding Zhou Fei Sheng-Nan Sun Zhao-Hui Zheng Ding Wei jun Jiang Jin-Lin Miao San-Zhong Li Xing Luo Kui Zhang Bin Wang Kun Zhang Su Pu Qian-Ting Wang Xin-Yue Zhang Gao-Liu Wen jun oliu John Thomas August Huijie Bian Zhi-Nan Chen You-Wen He Department of Clinical Immunology Xijing HospitalDepartment of Cell BiologyNational Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'an710032China Beijing Tricision Biotherapeutics Inc. Beijing100176China Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an710032China Zhuhai Tricision Biotherapuetics Inc. ZhuhaiGuangdong519040China Department of Pharmacology and Molecular Sciences Johns Hopkins University School of MedicineBaltimoreMD21205USA

Glioblastoma(GBM)is a lethal cancer with limited therapeutic *** cell(DC)-based cancer vaccines provide a promising approach for GBM *** studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor ***,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 *** patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor ***,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen *** treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC *** patient also received 28 doses of cyclophosphamide for depletion of regulatory T *** immunotherapy-related adverse events were observed during the *** antitumor CD4t and CD8t T-cell responses were *** patient remains free of disease *** is the first case report on the combination of the above three agents to treat glioblastoma *** results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

关键词： Glioblastoma multiforme DC vaccine Tumor-associated antigens Neoantigens

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Ethacrynic acid targets GSTM1 to ameliorate obesity by promoting browning of white adipocytes

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Protein & Cell 2021年第6期12卷 493-501页

作者： Zhaomeng Cui Yang Liu Wei Wan Yuyan Xu Yehui Hu Meng Ding Xin Dou Ruina Wang Hailing Li Yongmei Meng Wei Li Wei Jiang Zengxia Li Yiming Li Minjia Tan Dengke KMa Yu Ding jun oliu Cheng Luo Biao Yu Qiqun Tang Yongjun Dang Key Laboratory of Metabolism and Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologyShanghai Medical CollegeFudan UniversityShanghai 200030China Institute of Stem Cell Research and Regenerative Medicine Institutes of Biomedical SciencesFudan UniversityShanghai 200030China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Physiology and Biophysics School of Life SciencesFudan UniversityShanghai 200438China Henan Sesame Research Center Henan Academy of Agricultural SciencesZhengzhou 450002China College of Traditional Mongolian Medicine Inner Mongolia Medical UniversityMongolia 010110China State Key Laboratory of Bio-organic and Natural Products Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China Department of Endocrinology and Metabolism Huashan HospitalFudan UniversityShanghai 200040China Department of Physiology Cardiovascular Research InstituteUniversity of California San FranciscoSan FranciscoUSA Department of Pharmacology and Molecular Sciences The Johns Hopkins University School of MedicineBaltimoreMDUSA

Dear Editor,Obesity is caused by an imbalance between energy intake and expenditure,and has become a global epidemic with over 650 million adults *** tissues in mammals are composed of white adipose tissue(WAT)and classical brown adipose tissue(BAT),and their balance is highly related to the occurrence of *** browning of white adipocytes results in“beige”or“brite”adipocytes,which appear functionally similar to classical brown adipocytes,and can be detected in WAT deposits of animals that have been exposed to cold or other inducers(Fu et al.,2015).

关键词： GSTM1 obesity adipocyte

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Numerical investigation of non-uniform temperature fields for proppant and fluid phases in supercritical CO_(2)fracturing

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Particuology 2024年第7期90卷 149-163页

作者： Boyu Liu jun Yao Research Center of Multiphase Flow in Porous Media China University of Petroleum(East China)Qingdao 266000China

The non-uniform temperature distribution in supercritical CO_(2)(Sc-CO_(2))fracturing influences the density,viscosity,and volume expansion or shrinkage rate of Sc-CO_(2),impacting proppant *** study presents a coupled computational fluid dynamics-discrete element method and heat transfer model to examine the effects of proppant bed shape and the heat transfers of proppant-wall,proppant-fluid,and fluid-wall on the fluid and proppant temperature *** Sc-CO_(2)volume expansion is assessed under various temperature conditions by evaluating the volume-averaged Sc-CO_(2)*** factors,including proppant size,shape,thermal conductivity,concentration,temperature difference,and injection velocity,are carefully analyzed to elucidate their *** findings elucidate the existence of four distinct zones in the fluid temperature *** zone exhibits different magnitudes of temperature change under diverse conditions and undergoes dynamic transformations with the development of the proppant *** fluid-wall heat transfer and the fluid temperatures in Zones C and D are significantly subject to the fluid injection velocity(governing the heating duration),the temperature difference between fluid and formation(impacting the magnitude of heat flux),and the proppant bed shape(controlling the effective heating area).Additionally,the proppant-wall and proppant-fluid heat transfers determine the temperatures of both the proppant bed and the fluid within Zone B,showing a strong correlation with proppant thermal conductivity,proppant size,injection velocity,and temperature *** proposed coupled model provides valuable insights into the temperature distributions and flow behaviors of temperature-dependent fracturing fluids and proppants.

关键词： CFD-DEM Heat transfer Compressible fluid CO_(2)sequestration Proppant transport

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Geometric Error Identification of Gantry-Type CNC Machine Tool Based on Multi-Station Synchronization Laser Tracers

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 150-162页

作者： jun Zha Huijie Zhang School of Mechanical Engineering Xi’an Jiaotong UniversityXi’an 710049China Xi’an Jiaotong University Suzhou Academy Suzhou 215123China

Laser tracers are a three-dimensional coordinate measurement system that are widely used in industrial *** propose a geometric error identification method based on multi-station synchronization laser tracers to enable the rapid and high-precision measurement of geometric errors for gantry-type computer numerical control(CNC)machine *** method also improves on the existing measurement efficiency issues in the single-base station measurement method and multi-base station time-sharing measurement *** consider a three-axis gantry-type CNC machine tool,and the geometric error mathematical model is derived and established based on the combination of screw theory and a topological analysis of the machine kinematic *** four-station laser tracers position and measurement points are realized based on the multi-point positioning principle.A self-calibration algorithm is proposed for the coordinate calibration process of a laser tracer using the Levenberg-Marquardt nonlinear least squares method,and the geometric error is solved using Taylor’s first-order linearization *** experimental results show that the geometric error calculated based on this modeling method is comparable to the results from the Etalon laser *** a volume of 800 mm×1000 mm×350 mm,the maximum differences of the linear,angular,and spatial position errors were 2.0μm,2.7μrad,and 12.0μm,respectively,which verifies the accuracy of the proposed *** research proposes a modeling method for the precise measurement of errors in machine tools,and the applied nature of this study also makes it relevant both to researchers and those in the industrial sector.

关键词： Multi-point positioning Multi-station synchronization CNC machine tool Geometric error Error separation

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A generalized presentation of multi-caloric effects based on exterior derivative theory and its applications

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Communications in Theoretical Physics 2024年第8期76卷 156-163页

作者： jun Yin School of Materials Science and Engineering Nankai UniversityTianjin 300350China School of Mechanical Engineering and Automation Fuzhou UniversityFuzhou 350108China

The emerging concept of multi-caloric effects, introduced in 2010, entails the application of multiple interplay fields to a thermodynamic system. While multi-caloric effects are the main focus of experimental endeavors, theoretical considerations fall short of providing a thorough understanding. This paper introduces a comprehensive presentation on multi-caloric effects,employing the method and theory of exterior derivative formations. It addresses every aspect of thermodynamic systems, showcasing its applicability to multi-caloric materials(both singlephase and multi-phase materials), and its adaptability to different scenarios(either in single or multiple force fields). The formulation of Maxwell relationships, characterized by their generality and universality, enables a clear prediction in entropy and temperature, facilitating a distinct identification between independent and interdependent contributions from multi-caloric effects. These insights hold significant importance in designing and developing specialized thermodynamic materials, optimizing functional performances and exploring innovative mechanisms.

关键词： multicaloric effects Maxwell relations isothermal entropy adiabatic temperature

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On the Monge–Kantorovich Mass Transfer Problem in Higher Dimensions

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Acta Mathematica Sinica,English Series 2024年第8期40卷 1989-2004页

作者： Xiao jun LU School of Mathematics Southeast UniversityNanjing 210096P.R.China

This paper mainly investigates the approximation of a global maximizer of the Monge–Kantorovich mass transfer problem in higher dimensions through the approach of nonlinear partial differential equations with Dirichlet *** an approximation mechanism,the primal maximization problem can be transformed into a sequence of minimization *** applying the systematic canonical duality theory,one is able to derive a sequence of analytic solutions for the minimization *** the final analysis,the convergence of the sequence to an analytical global maximizer of the primal Monge–Kantorovich problem will be demonstrated.

关键词： Monge-Kantorovich mass transfer singular variational problem canonical duality theory

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Effect of Wave Nonlinearity on the Instantaneous Seabed Liquefaction

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China Ocean Engineering 2024年第1期38卷 93-103页

作者： WANG Zhao-jun SUI Ti-ti ZHANG Chi PAN jun-ning Key Laboratory of Port Waterway and Sedimentation Engineering of the Ministry of TransportNanjing Hydraulic Research InstituteNanjing 210024China Key Laboratory of Coastal Disaster and Protection(Hohai University) Ministry of EducationNanjing 210098China The National Key Laboratory of Water Disaster Prevention Nanjing 210098China

The nonlinear variation of wave is commonly seen in nearshore area,and the resulting seabed response and liquefaction are of high concern to coastal *** this study,an analytical formula considering the nonlinear wave skewness and asymmetry is adopted to provide wave pressure on the seabed *** liquefaction depth attenuation coefficient and width growth coefficient are defined to quantitatively characterize the nonlinear effect of wave on seabed *** on the 2D full dynamic model of wave-induced seabed response,a detailed parametric study is carried out in order to evaluate the influence of the nonlinear variation of wave loadings on seabed ***,new empirical prediction formulas are proposed to fast predict the maximum liquefaction under nonlinear *** indicate that(1)Due to the influence of wave nonlinearity,the vertical transmission of negative pore water pressure in the seabed is hindered,and therefore,the amplitude decreases significantly.(2)In general,with the increase of wave nonlinearity,the liquefaction depth of seabed decreases *** under asymmetric and skewed wave loading,the attenuation of maximum seabed liquefaction depth is the most significant among all the nonlinear wave ***,highly skewed wave can cause the liquefaction depth of seabed greater than that under linear wave.(3)The asymmetry of wave pressure leads to the increase of liquefaction width,whereas the influence of skewedness is not significant.(4)Compared with the nonlinear waveform,seabed liquefaction is more sensitive to the variation of nonlinear degree of wave loading.

关键词： nonlinear wave seabed response seabed liquefaction numerical simulation liquefaction prediction

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Survey on performance of vertical slot and nature-like fishways at Angu hydropower station, Southwest China

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Water Science and Engineering 2024年第1期17卷 83-91页

作者： jun-jian Sun Jia-yue Shi Qi Zhang Xiao-tao Shi jun-jun Tan PowerChina Huadong Engineering Corporation Limited Hangzhou 311122China Hubei International Science and Technology Cooperation Base of Fish Passage China Three Gorges UniversityYichang 443002China

To restore dam-blocked natural fish migratory passages,a growing number of artificial fishways have been built in water conservancy and hydropower projects in *** Angu hydropower station involved diverse important fish habitats in the lower reaches of the Daduhe River in Southwest ***,a vertical slot fishway(VSF)and a nature-like fishway(NLF)were built near the backwater area of the reservoir to connect the upstream and downstream *** and aquatic ecological surveys were conducted after the completion of the project to estimate the fish passing effect of the two *** results indicated that both fishways were in effective operation and could maintain the desired hydrodynamic conditions and be used by several local fish *** the survey,149 fish from 15 species and 111 fish from 17 species were captured by the traps in the VSF and NLF,respectively,while 1263 fish from 27 species were found in the downstream *** species captured in the VSF were not found in the NLF,and vice versa,which implied the different preferences of ***,3789 signals including 2099 upward ones and 1690 downward ones were monitored with an ultrasonic fish detector at the inlet of the *** findings revealed the characteristics of fish species observed in and near the fishways and provided valuable insights into the different fish passing capabilities of VSFandNLF.

关键词： Vertical slot fishway Nature-like fishway Aguatic ecological survey Fishwaymonitoring Statistical analysis

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Immunotherapy for hepatocellular carcinoma

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中华医学杂志(英文版) 2024年第15期137卷 1765-1776页

作者： Wang Xiaoxia Lu jun Department of Medical Oncology Beijing YouAn Hospital Capital Medical University Beijing China Laboratory for Clinical Medicine Capital Medical University Beijing China

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Its high recurrence rate and lack of effective control drugs result in a 5-year survival rate of only about 10%. HCC is a tumor regulated by the immune system. Significant breakthroughs have occurred in treating solid tumors with immunotherapy in recent years. Various immunotherapies, such as immune checkpoint inhibitors (ICIs), including combination therapies, have demonstrated promising therapeutic effects in both clinical applications and research. Other immunotherapies, such as adoptive cell therapies and oncolytic viruses, are also emerging, offering hope for addressing long-term survival issues in HCC. This article reviews current commonly used immunotherapy strategies and the latest research findings for reference.

关键词： Immunotherapy Immune checkpoint inhibitors Adoptive cell therapies Hepatocellular carcinoma

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Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： jun Sun Yinglin Xia Division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological *** is emerging as a powerful tool generally for pre-cision ***,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and ***,metabo-lomics data are very ***/pretreating and normalizing procedures on metabolomics data are usually required before statistical *** this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data *** discuss the advantages and limitations of each *** choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis *** then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

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