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DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & Medicine 2024年第3期21卷 252-266页

作者： Junya Yan Shibo Wang Jing Zhang Qiangqiang Yuan Xianchun Gao Nannan Zhang Yan pan Haohao Zhang Kun Liu Jun Yu Linbin Lu Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila Yu Qi Qiujin Zhang Shundong Cang Yuanyuan Lu Yanglin pan Yan Kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China Unit 73211 of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese Medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

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Efficacy of scraping therapy on blood pressure and sleep quality in stage Ⅰ and Ⅱ essential hypertension: A systematic review and meta-analysis

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Journal of Integrative Medicine 2024年第1期22卷 12-21页

作者： Zheng-gang Zhu Jian-ru Wang Xiao-yan pan School of Nursing Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina School of Health Sciences Universiti Sains MalaysiaKubang Kerian 16150KelantanMalaysia Department of Cardiovascular Medicine the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 450000Henan ProvinceChina

Background Scraping therapy is widely used in treating stage I and II essential hypertension in China.However,there has been no systematic evaluation of the efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension.Search strategy Seven electronic databases(PubMed,Scopus,Cochrane Library,Web of Science,EBSCO,China National Knowledge Infrastructure and Wanfang Data electronic databases)were searched from inception to December 2022.Based on the principle of combining subject words with text words,the search strategy was constructed around search terms for“scraping therapy,”“scraping,”“Guasha,”“Gua sha,”“hypertension,”and“high blood pressure”during the database searches.Inclusion criteria Randomized controlled trials(RCTs)were included if they recruited patients with stage I and II essential hypertension and included a scraping therapy intervention.The intervention group received antihypertensive drugs and scraping therapy,while the control group only took antihypertensive drugs.Data extraction and analysis Review Manager 5.4.0 and STATA 15.1 were used to enter all the relevant outcome variables to conduct the meta-analysis.The quality of the selected RCTs was assessed using the PEDro scale.The sensitivity analysis was carried out by iteratively excluding individual studies and repeating the analysis to determine the stability of the findings and identify any studies with greater influence on the outcome.Subgroup analysis was performed to find the source of heterogeneity.Funnel plots were used to evaluate the publication bias of included studies.Results Nine RCTs including 765 participants were selected.Meta-analysis showed that scraping therapy combined with medication had an advantage over the use of medication alone in lowering systolic blood pressure(mean difference[MD]=?5.09,95%confidence interval[CI]=?6.50 to?3.67,P<0.001)and diastolic blood pressure(MD=?2.66,95%CI=?3.17 to?2.14,P<0.001).Subgroup analysis showed that scraping therapy improved sleep quality in mid

关键词： Scraping therapy Essential hypertension Efficacy Blood pressure Sleep quality Systematic review Meta-analysis

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Electron beam lithography on nonplanar and irregular surfaces

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Microsystems & Nanoengineering 2024年第2期10卷 1-23页

作者： Chenxu Zhu Huseyin Ekinci Aixi pan Bo Cui Xiaoli Zhu Department of Electrical and Computer Engineering and Waterloo Institute for Nanotechnology(WIN) University of WaterlooWaterlooONCanada

E-beam lithography is a powerful tool for generating nanostructures and fabricating nanodevices with fine features approaching a few nanometers in size.However,alternative approaches to conventional spin coating and development processes are required to optimize the lithography procedure on irregular surfaces.In this review,we summarize the state of the art in nanofabrication on irregular substrates using e-beam lithography.To overcome these challenges,unconventional methods have been developed.For instance,polymeric and nonpolymeric materials can be sprayed or evaporated to form uniform layers of electron-sensitive materials on irregular substrates.Moreover,chemical bonds can be applied to help form polymer brushes or self-assembled monolayers on these surfaces.In addition,thermal oxides can serve as resists,as the etching rate in solution changes after e-beam exposure.Furthermore,e-beam lithography tools can be combined with cryostages,evaporation systems,and metal deposition chambers for sample development and lift-off while maintaining low temperatures.Metallic nanopyramids can be fabricated on an AFM tip by utilizing ice as a positive resistor.Additionally,Ti/Au caps can be patterned around a carbon nanotube.Moreover,3D nanostructures can be formed on irregular surfaces by exposing layers of anisole on organic ice surfaces with a focused e-beam.These advances in e-beam lithography on irregular substrates,including uniform film coating,instrumentation improvement,and new pattern transferring method development,substantially extend its capabilities in the fabrication and application of nanoscale structures.

关键词： lithography beam coating

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Azocalixarenes: a scaffold of universal excipients with high efficiency

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Science China Chemistry 2024年第5期67卷 1697-1706页

作者： Yu-xin Yue Yi-Lin Lin Meng-Meng Chen Han-Wen Tian Rong Ma Ze-Han Wang Fang-Yuan Chen Yu-Chen pan Dong-Sheng Guo College of Chemistry State Key Laboratory of Elemento-Organic ChemistryKey Laboratory of Functional Polymer Materials(Ministry of Education)Frontiers Science Center for New Organic MatterCollaborative Innovation Center of Chemical Science and Engineering(Tianjin)Nankai UniversityTianjin 300071China

Excipients are important components of pharmaceutical preparations that affect their quality, safety, and efficacy. Macrocyclic receptors are a family of supramolecular excipients with several advantages, including molecular-level protection, small sizes,fast kinetics of host-guest recognition, and modular construction. With the continuous advances in the medical field, personalized and precision medicine requires the development of excipients with low dosages, integrated modifying effects, universality,and controlled release. To meet these requirements, we have developed a new family of macrocyclic excipients based on calixarenes by integrating their covalent(broad chemical design space) and noncovalent(wide range of substrates) advantages.Accordingly, azocalixarenes(Azo CAs) were designed, showing high binding affinities to a broad spectrum of active pharmaceutical ingredients(APIs), selectivity to interferents, and responsiveness to hypoxic microenvironments. Due to their highly efficient and controllable recognition, Azo CAs serve as low-dose excipients for 30 APIs. Molecular encapsulation by Azo CAs results in the integrated modification of the physicochemical properties of APIs, including solubility, stability, bioavailability,and biocompatibility. Moreover, Azo CAs can be reduced by azoreductases overexpressed in hypoxic microenvironments,leading to the controlled release of APIs. Collectively, Azo CA excipients have broad application prospects for a series of diseases such as enteritis, arthritis, stroke, cancer, bacterial infection and kidney injury, with diverse therapeutic modalities,including chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, boron neutron capture therapy, radiotherapy, fluorescence imaging, and their combinations.

关键词： supramolecular chemistry host-guest systems excipient calixarene molecular recognition

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Unveiling non-radiative center control in CsPbBr_(3) nanocrystals:A comprehensive comparative analysis of hot injection and ligandassisted reprecipitation approaches

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Nano Research 2024年第5期17卷 4525-4534页

作者： Daocheng hong Yuchen Zhang Shuhan pan Hanyu Liu Wei Mao Wanli Zhang Yuhui Ye Zhihong Wei Xuxing Lu Xiaoyong Wang Zhenda Lu Yuxi Tian Key Laboratory for Advanced Technology in Environmental Protection of Jiangsu Province Yancheng Institute of TechnologyYancheng 224051China Laboratory of Mesoscopic Chemistry of MOE School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China College of Engineering and Applied Sciences Nanjing UniversityNanjing 210023China National Laboratory of Solid State Microstructures School of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China School of Electronic Electrical Engineering and PhysicsFujian University of TechnologyFuzhou 350118China

Metal-halide perovskite nanocrystals(NCs)have gained significant attention in the field of optoelectronic and photonic devices due to their promising applications.Despite their exceptional optical properties,the impact of different synthetic strategies on the fundamental nature of NCs,such as nonradiative recombination centers,remains poorly understood.In this study,we investigated the photophysical properties of CsPbBr_(3) NCs synthesized using two distinct methods,hot injection and ligand-assisted reprecipitation,at the individual particle level.We observed different blinking behaviors under specific photoexcitation power densities and proposed,through intensity-lifetime analysis and Monte-Carlo simulations,that these different synthetic strategies can fabricate NCs with similar crystal structures but distinct surface quenchers with varying energy levels,which significantly affected the photo-induced blinking-down and blinking-up behaviors in individual NCs.Our findings indicate a practical and feasible approach for controlling defect engineering in perovskite NCs,with significant implications for their use in optoelectronic and other technological applications.

关键词： metal-halide perovskite nanocrystals photophysical properties nonradiative recombination centers hot injection method ligand-assisted reprecipitation

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Channel Estimation for Reconfigurable Intelligent Surface Aided Multiuser Millimeter-Wave/THz Systems

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China Communications 2024年第3期21卷 91-103页

作者： Chu hongyun pan Xue Li Baijiang School of Communications and Information Engineering Xi’an University of Posts and TelecommunicationsXi’an 710121China

It is assumed that reconfigurable intelligent surface(RIS)is a key technology to enable the potential of mmWave communications.The passivity of the RIS makes channel estimation difficult because the channel can only be measured at the transceiver and not at the RIS.In this paper,we propose a novel separate channel estimator via exploiting the cascaded sparsity in the continuously valued angular domain of the cascaded channel for the RIS-enabled millimeter-wave/Tera-Hz systems,i.e.,the two-stage estimation method where the cascaded channel is separated into the base station(BS)-RIS and the RIS-user(UE)ones.Specifically,we first reveal the cascaded sparsity,i.e.,the sparsity exists in the hybrid angular domains of BS-RIS and the RIS-UEs separated channels,to construct the specific sparsity structure for RIS enabled multi-user systems.Then,we formulate the channel estimation problem using atomic norm minimization(ANM)to enhance the proposed sparsity structure in the continuous angular domains,where a low-complexity channel estimator via Alternating Direction Method of Multipliers(ADMM)is proposed.Simulation findings demonstrate that the proposed channel estimator outperforms the current state-of-the-arts in terms of performance.

关键词： atomic norm minimization cascaded channel estimation convex optimization mmWave/THz reconfigurable intelligent surface(RIS) sparsity

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Experimental Investigation of the Operating Characteristics of a Pulsating Heat Pipe with Ultra-Pure Water and Micro Encapsulated Phase Change Material Suspension

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Journal of Thermal Science 2024年第2期33卷 457-468页

作者： SHI Weixiu SU Xiaoyang CHEN hongdi pan Lisheng Beijing Engineering Research Center of Sustainable Energy and Buildings Beijing University of Civil Engineering and ArchitectureBeijing100044China School of Environment and Energy Engineering Beijing University of Civil Engineering and ArchitectureBeijing100044China State Key Laboratory of High Temperature Gas Dynamics Institute of MechanicsChinese Academy of SciencesBeijing100190China

The specific heat capacity of working fluid is an important influence factor on heat transfer characteristic of the pulsating heat pipe(PHP).Due to the relatively large specific heat capacity of micro encapsulated phase change material(MEPCM) suspension,a heat transfer performance experimental facility of the PHP was established.The heat transfer characteristic with MEPCM suspension of different mass concentrations(0.5% and 1.0%) and ultra-pure water were compared experimentally.It was found that when the PHP uses MEPCM suspension as its working fluid,operating stability is impoverished under lower heating power and the operating stability is better under higher heating power.At the inclination angle of 90°,the temperature at heating side decreases compared to ultra-pure water and the temperature at heating side decreases with the raising of MEPCM suspension mass concentration.The heat transfer characteristic of the PHP is positively correlated with the inclination angle and the 90° is optimum.The unfavorable effect of the inclination angle decreases with heating power increasing.When the inclination angle is 90°,the PHP with MEPCM suspension at 1.0% of mass concentration has the lowest thermal transfer resistance and followed by ultra-pure water and MEPCM suspension at 0.5% of mass concentration has the highest thermal transfer resistance.When the inclination angles are 60° and30°,the effect of gravity on the flow direction is reduced to 86.6% and 50% of that on the inclination angle of 90°,respectively,and the promoting effect of gravity on the working fluid is further weakened as the inclination angle further decreases.Due to the high viscosity of MEPCM suspension,the PHP with ultra-pure water has the lowest heat transfer resistance.When the inclination angles is 60°,the thermal resistance with MEPCM suspension at0.5% of the mass concentration is lower than that at 1.0% at the heating power below 230 W.The thermal resistance of MEPCM suspension tends to be similar for heating power of 230-250 W.At the heating

关键词： pulsating heat pipe(PHP) micro encapsulated phase change material(MEPCM) heat transfer characteristic inclination angle

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SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian Chen-hong Ding Fang Liu Shi-Jie Chen Chen-Kai Huang Meng-Chao Xiao Xia-Lu hong Ming-Chen Wang Fang-Zhi Yan Kai Ding Ya-Lu Cui Bai-Nan Zheng Jin Ding Cheng Luo xin Zhang Wei-Fen Xie Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug Discovery and Design Center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of Gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression.However,the precise molecular mechanisms governing the nuclear import of YAP are not fully understood.In this study,we have uncovered a crucial role of SOX9 in the activation of YAP.SOX9 promotes the nuclear translocation of YAP by direct interaction.Importantly,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP.Additionally,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by PRMT1.YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers.Furthermore,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth.This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction. interaction precise

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The Al_(2)O_(3)and Mn/Al_(2)O_(3)sorbents highly utilized in destructive sorption of NF_(3)

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Chinese Journal of Chemical Engineering 2024年第1期65卷 54-62页

作者： Yanfei pan Hejian Li Li Zheng Xiufeng Xu School of Chemistry and Chemical Engineering Yantai UniversityYantai 264005China

NF_(3)is commonly used as an etching and cleaning gas in semiconductor industry,however it is a strongly greenhouse gas.Therefore,the destruction of disposal NF_(3)is an urgent task to migrate the greenhouse effect.Among the technologies for NF_(3)abatement,the destructive sorption of NF_(3)over metal oxides sorbents is an effective way.Thus,the search for a highly reactive and utilized sorbent for NF_(3)destruction is in great demand.In this work,AlOOH supported on carbon-sphere(AlOOH/CS)as precursors were synthesized hydrothermally and heat-treated to prepare the Al_(2)O_(3)sorbents.The influence of AlOOH/CS hydrothermal temperatures on the reactivity of derived Al_(2)O_(3)sorbents for NF_(3)destruction was investigated,and it is shown that the Al2O3 from AlOOH/CS hydro-thermalized at 120℃is superior to others.Subsequently,the optimized Al_(2)O_(3)was covered by Mn(OH)x to prepare Mn/Al_(2)O_(3)sorbents via changing hydrothermal temperatures and Mn loadings.The results show that the Mn/Al_(2)O_(3)sorbents are more utilized than bare Al_(2)O_(3)in NF_(3)destructive sorption due to the promotional effect of Mn_(2)O_(3)as surface layer on the fluorination of Al_(2)O_(3)as substrate,especially the optimal 5%Mn/Al2O3(160℃)exhibits a utilization percentage as high as 90.4%,and remarkably exceeds all the sorbents reported so far.These findings are beneficial to develop more efficient sorbents for the destruction of NF_(3).

关键词： Greenhouse gas NF_(3)destructive sorption Sorbents Al_(2)O_(3) Mn/Al_(2)O_(3) Reactivity

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A reduced-order model for fast predicting ionized flows of hypersonic vehicles along flight trajectory

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Chinese Journal of Aeronautics 2024年第1期37卷 89-105页

作者： Jingchao ZHANG Chunsheng NIE Jinsheng CAI Shucheng pan School of Aeronautics Northwestern Polytechnical UniversityXi’an 710072China Science and Technology on Space Physics Laboratory China Academy of Launch Vehicle TechnologyBeijing 100076China Institute of Extreme Mechanics Northwestern Polytechnical UniversityXi’an 710072China

An improved Reduced-Order Model(ROM)is proposed based on a flow-solution preprocessing operation and a fast sampling strategy to efficiently and accurately predict ionized hypersonic flows.This ROM is generated in low-dimensional space by performing the Proper Orthogonal Decomposition(POD)on snapshots and is coupled with the Radial Basis Function(RBF)to achieve fast prediction speed.However,due to the disparate scales in the ionized flow field,the conventional ROM usually generates spurious negative errors.Here,this issue is addressed by performing flow-solution preprocessing in logarithmic space to improve the conventional ROM.Then,extra orthogonal polynomials are introduced in the RBF interpolation to achieve additional improvement of the prediction accuracy.In addition,to construct high-efficiency snapshots,a trajectory-constrained adaptive sampling strategy based on convex hull optimization is developed.To evaluate the performance of the proposed fast prediction method,two hypersonic vehicles with classic configurations,i.e.a wave-rider and a reentry capsule,are used to validate the proposed method.Both two cases show that the proposed fast prediction method has high accuracy near the vehicle surface and the free-stream region where the flow field is smooth.Compared with the conventional ROM prediction,the prediction results are significantly improved by the proposed method around the discontinuities,e.***.the shock wave and the ionized layer.As a result,the proposed fast prediction method reduces the error of the conventional ROM by at least 45%,with a speedup of approximately 2.0×105compared to the Computational Fluid Dynamic(CFD)simulations.These test cases demonstrate that the method developed here is efficient and accurate for predicting ionized hypersonic flows.

关键词： Reduced-order model Radial basis function Constrained sampling Transfer function Fast flow prediction Ionized hypersonic flows

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