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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Copper homeostasis and neurodegenerative diseases

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Neural Regeneration research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang International research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Development of a deviation package method for low-cost robust optimization in compressor blade design

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Chinese Journal of Aeronautics 2024年第4期37卷 166-180页

作者： Mingzhi LI Xianjun YU Dejun MENG Guangfeng AN Baojie LIU research Institute of Aero-engine Beihang UniversityBeijing 100191China National Key Laboratory of Science&Technology on Aero-engine Aero-Thermodynamics Beihang UniversityBeijing 100191China AECC Shenyang engine research Institute Shenyang 110015China

Manufacture variations can greatly increase the performance variability of compressor blades. Current robust design optimization methods have a critical role in reducing the adverse impact of the variations, but can be affected by errors if the assumptions of the deviation models and distribution parameters are inaccurate. A new approach for robust design optimization without the employment of the deviation models is proposed. The deviation package method and the interval estimation method are exploited in this new approach. Simultaneously, a stratified strategy is used to reduce the computational cost and assure the optimization accuracy. The test case employed for this study is a typical transonic compressor blade profile, which resembles most of the manufacture features of modern compressor blades. A set of 96 newly manufactured blades was measured using a coordinate measurement machine to obtain the manufacture variations and produce a deviation package. The optimization results show that the scatter of the aerodynamic performance for the optimal robust design is 20% less than the baseline value. By comparing the optimization results obtained from the deviation package method with those obtained from widely-used methods employing the deviation model, the efficiency and accuracy of the deviation package method are demonstrated. Finally, the physical mechanisms that control the robustness of different designs were further investigated, and some statistical laws of robust design were extracted.

关键词： Manufacture variations Robust design optimization Compressor leading edge Aerodynamics Physical mechanism

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Large eddy simulation of turbulent premixed and stratified combustion using flame surface density model coupled with tabulation method

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Applied Mathematics and Mechanics(English Edition) 2018年第12期39卷 1719-1736页

作者： Zhou YU Hongda ZHANG Taohong YE Minming ZHU Department of Thermal Science and Energy engineering University of Science and Technology of China Shenyang engine research Institute Aero Engine (Group) Corporation of China

Large eddy simulations(LESs) are performed to investigate the Cambridge premixed and stratified flames, SwB1 and SwB5, respectively. The flame surface density(FSD) model incorporated with two different wrinkling factor models, i.e., the Muppala and Charlette2 wrinkling factor models, is used to describe combustion/turbulence interaction, and the flamelet generated manifolds(FGM) method is employed to determine major scalars. This coupled sub-grid scale(SGS) combustion model is named as the FSD-FGM model. The FGM method can provide the detailed species in the flame which cannot be obtained from the origin FSD model. The LES results show that the FSD-FGM model has the ability of describing flame propagation, especially for stratified flames. The Charlette2 wrinkling factor model performs better than the Muppala wrinkling factor model in predicting the flame surface area change by the *** combustion characteristics are analyzed in detail by the flame index and probability distributions of the equivalence ratio and the orientation angle, which confirms that for the investigated stratified flame, the dominant combustion modes in the upstream and downstream regions are the premixed mode and the back-supported mode, respectively.

关键词： large eddy simulation(LES) flame surface density(FSD) model tabulation premixed combustion stratified combustion

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Large eddy simulation of turbulent premixed piloted flame using artificial thickened flame model coupled with tabulated chemistry

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Applied Mathematics and Mechanics(English Edition) 2018年第9期39卷 1277-1294页

A sub-grid scale(SGS) combustion model, which combines the artificial thickened flame(ATF) model with the flamelet generated manifold(FGM) tabulation method, is proposed. Based on the analysis of laminar flame structures, two self-contained flame sensors are used to track the diffusion and reaction processes with different spatial scales in the flame front, respectively. The dynamic formulation for the proposed SGS combustion model is also performed. Large eddy simulations(LESs) of Bunsen flame F3 are used to evaluate the different SGS combustion models. The results show that the proposed SGS model has the ability in predicting the distributions of temperature and velocity reasonably, while the predictions for the distributions of some species need further improvement. The snapshots of instantaneous normalized progress variables reveal that the flame is more remarkably and severely wrinkled at the flame tip for flame *** satisfactory results obtained by the dynamic model indicate that it can preserve the premixed flame propagation characteristics better.

关键词： large eddy simulation(LES) artificial thickened flame model tabulation dynamic modeling flame sensor

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Turbulent characteristics and rotation correction of wall function in rotating channel with high local rotation parameter

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Chinese Journal of Aeronautics 2018年第10期31卷 1985-1999页

作者： Zhi TAO Huijie WU Ruquan YOU Haiwang LI Kuan WEI National Key Laboratory of Science and Technology on Aero-engine Aero-Thermodynamics Beihang University Collaborative Innovation center for Advanced Aero-engine Beihang University

The turbulent fluctuation and the rotation correction of wall function law are investigated in the entrance section of a rotating channel. The one-dimensional hot wire probe and the X-type probe are utilized to measure the boundary layer at four streamwise stations. Through the analysis on the boundary layer near the leading side and trailing side, it is found that the turbulent fluctuation is promoted in the trailing side whereas suppressed in the leading side. This difference is attributed to the Coriolis instability near the trailing side. In addition, considering the local rotation parameter Rc, whose maximum absolute value is 0.014, is larger than that in previous research, whose maximum value is 0.007, the whole process of the relaminarization is captured. To understand this phenomenon better, the effects of the generation term and the Coriolis term in the transport equation of the Reynolds stress are discussed. In addition, the rotation correction of the viscous-Coriolis region and the Coriolis region are discussed, a new revising method for the wall function is proposed.

关键词： Coriolis force Entry section Relaminarization Rotating channel Turbulence

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Experimental investigation of surface roughness effects on flow behavior and heat transfer characteristics for circular microchannels

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Chinese Journal of Aeronautics 2016年第6期29卷 1575-1581页

作者： Yuan Xing Tao Zhi Li Haiwang Tian Yitu National Key Laboratory of Science and Technology on Aero-engine Beihang University Collaborative Innovation center for Advanced Aero-engine of China of Aerodynamics Beihang University

This paper experimentally investigates the effect of surface roughness on flow and heat transfer characteristics in circular microchannels. All test pieces include 44 identical, parallel circular microchannels with diameters of 0.4 mm and 10 mm in length. The surface roughness of the microchannels is R= 0.86, 0.92, 1.02 lm, and the Reynolds number ranges from 150 to *** show that the surface roughness of the circular microchannels has remarkable effects on the performance of flow behavior and heat transfer. It is found that the Poiseuille and Nusselt numbers are higher when the relative surface roughness is larger. For flow behavior, the friction factor increases consistently with the increasing Reynolds number, and it is larger than the constant theoretical value for macrochannels. The Reynolds number for the transition from laminar to turbulent flow is about 1500, which is lower than the value for macrochannels. For the heat transfer property, Nusselt number also increases with increasing Reynolds number, and larger roughness contributes to higher Nusselt number.

关键词： Circular Flow behavior Heat transfer Microchannels Roughness

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Constructing Donor–Acceptor‑Linked COFs Electrolytes to Regulate Electron Density and Accelerate the Li^(+)Migration in Quasi‑Solid‑State Battery

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Nano-Micro Letters 2025年第1期17卷 456-471页

作者： Genfu Zhao Hang Ma Conghui Zhang Yongxin Yang Shuyuan Yu Haiye Zhu Yongjiang Sun Hong Guo School of Materials and Energy International Joint Research Center for Advanced Energy Materials of Yunnan ProvinceYunnan UniversityKunming 650091People’s Republic of China Yunnan Yuntianhua Co. LtdR&D CenterKunming 650228People’s Republic of China Southwest United Graduate School Kunming 650091People’s Republic of China

Regulation the electronic density of solid-state electrolyte by donor–acceptor(D–A)system can achieve highly-selective Li^(+)transportation and conduction in solid-state Li metal *** study reports a high-performance solid-state electrolyte thorough D–A-linked covalent organic frameworks(COFs)based on intramolecular charge transfer *** other reported COFbased solid-state electrolyte,the developed concept with D–A-linked COFs not only achieves electronic modulation to promote highly-selective Li^(+)migration and inhibit Li dendrite,but also offers a crucial opportunity to understand the role of electronic density in solid-state Li metal *** introduced strong electronegativity F-based ligand in COF electrolyte results in highlyselective Li^(+)(transference number 0.83),high ionic conductivity(6.7×10^(-4)S cm^(−1)),excellent cyclic ability(1000 h)in Li metal symmetric cell and high-capacity retention in Li/LiFePO_(4)cell(90.8%for 300 cycles at 5C)than substituted C-and N-based *** is ascribed to outstanding D–A interaction between donor porphyrin and acceptor F atoms,which effectively expedites electron transferring from porphyrin to F-based ligand and enhances Li^(+)***,we anticipate that this work creates insight into the strategy for accelerating Li^(+)conduction in high-performance solid-state Li metal batteries through D–A system.

关键词： Electronic modulation engineering Donor-acceptor-linked covalent organic frameworks Quasi-solid-state Li metal battery

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama center for Brain research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

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