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Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids

Protein & Cell 2024年第4期15卷 285-304页

作者： Yunuo Mao wei Wang Jingwei Yang Xin zhou Yongqu Lu Junpeng Gao Xiao Wang Lu Wen wei Fu Fuchou Tang School of Life sciences Biomedical Pioneering Innovation CenterDepartment of General SurgeryThird HospitalPeking UniversityBeijing 100871China beijing Advanced Innovation Center for Genomics(ICG) Ministry of Education Key Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Peking-Tsinghua Center for Life sciences Peking UniversityBeijing 100871China Peking University Third Hospital Cancer Center Beijing 100871China The Research Center of Stem Cell and Regenerative Medicine School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Colorectal cancer(CRC)is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be ***,we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original *** efficiently identify repurposed drugs for CRC,we developed a robust organoid-based drug screening *** combining the repurposed drug library and computation-based drug prediction,335 drugs were tested and 34.drugs with anti-CRC effects were *** importantly,we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns:differentiation induction,growth inhibition,metabolism inhibition,immune response promotion,and cell cycle *** anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft(PDOX)system in *** found that fedratinib,trametinib,and bortezomib exhibited effective anticancer ***,the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were *** study offers an innovative approach for drug discovery,and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.

关键词： colorectal cancer organoids drug repurposing patient-derived organoids-based xenograft mechanism of action

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Pre-mating nitenpyram exposure in male mice leads to depression-like behavior in offspring by affecting tryptophan metabolism in gut microbiota

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Journal of Environmental sciences 2024年第3期137卷 120-130页

作者： Sen Yan wei Sun Sinuo Tian Zhiyuan Meng Jinling Diao Zhiqiang zhou Li Li Wentao Zhu Innovation Center of Pesticide Research Department of Applied ChemistryCollege of ScienceChina Agricultural UniversityBeijing 100193China College of Plant Protection/Joint International Research Laboratory of Agriculture&Agri-Product Safety Yangzhou UniversityYangzhou 225009China College of Plant Protection Shanxi Agricultural UniversityTaiyuan 030031China

Several studies have confirmed that the health status of the paternal affects the health of the offspring,however,it remains unknown whether paternal exposure to pesticides affect the offspring ***,we used untargeted metabolomics and 16S rRNA sequencing technology,combined with tail suspension test and RT-qPCR to explore the effects of paternal exposure to nitenpyram on the neurotoxicity of *** results found that the paternal exposure to nitenpyram led to the offspring’s depressive-like behaviors,accompanied by the reduction of tryptophan content and the disorder of microbial abundance in the gut of the ***,we determined the expression of tryptophan metabolism-related genes tryptophanase(tnaA)and tryptophan hydroxylase 1(TpH1)in gut bacteria and colonic *** found that tryptophan is metabolized to indoles rather than being absorbed into colonocytes,which coursed the reduce of tryptophan availability after nitenpyram *** conclusion,our study deepens our understanding of the intergenerational toxic effects of pesticides.

关键词： Nitenpyram Depressive-like behaviors Gut microbiota Tryptophan metabolism

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Sensing-Assisted Accurate and Fast Beam Management for Cellular-Connected mmWave UAV Network

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China Communications 2024年第6期21卷 271-289页

作者： Cui Yanpeng Zhang Qixun Feng Zhiyong Qin Wen zhou Ying wei Zhiqing Zhang Ping School of Information and Communication Engineering Beijing University of Posts and TelecommunicationsBeijing 100876China School of Computer Science Northwestern Polytechnical UniversityXi’an 710072China

Beam management,including initial access(IA)and beam tracking,is essential to the millimeter-wave Unmanned Aerial Vehicle(UAV)***,the conventional communicationonly and feedback-based schemes suffer a high delay and low accuracy of beam alignment,since they only enable the receiver to passively“hear”the information of the transmitter from the radio *** paper presents a novel sensing-assisted beam management approach,the first solution that fully utilizes the information from the visual domain to improve communication *** employ both integrated sensing and communication and computer vision techniques and design an extended Kalman filtering method for beam tracking and ***,we also propose a novel dual identity association solution to distinguish multiple UAVs in dynamic ***-world experiments and numerical results show that the proposed solution outperforms the conventional methods in IA delay,association accuracy,tracking error,and communication performance.

关键词： beam management integrated sensing and communication UAV communication

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A review on adhesion behavior of chip seal pavement and aggregate

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第3期11卷 441-466页

作者： Yuming zhou Zhuyi Peng Jinyu Wang Jianguo wei Hao Liu Di Wang Jinming Li Key Laboratory of Road Structure and Material of Ministry of Transport(Changsha) Changsha University of Science and TechnologyChangsha 410114China School of Traffic and Transportation Engineering Changsha University of Science and TechnologyChangsha 410114China Wuhan Huike Testing Co. Ltd.Wuhan 430000China Department of Civil Engineering University of OttawaON KIN 6N5Canada CCCC Infrastructure Maintenance Group Co. Ltd.Beijing 100102China

Chip seal is widely used for preventive maintenance to mitigate pavement deterioration,but it is prone to aggregate loss during pavement *** further promote the development and application of chip seals in road engineering in China,the research progress of the adhesion behavior of aggregate and binder in chip seals was reviewed in this paper,focusing on the adhesion mechanism of emulsified asphalt and alkaline *** Influencing factors and evaluation methodology of chip seals'aggregate adhesion behavior were also *** results demonstrate that the adhesion process between emulsified asphalt and alkaline aggregate is divided into three processes including infiltration,demulsification,and cluster,which is more complicated when compared to hot *** designing a chip seal,not only the characteristics of single material should be paid attention to,but also the combination of binder and aggregate matters a *** form good adhesion between aggregate and asphalt binder,various influencing factors such as material selection,design method,and construction technical index should be considered comprehensively in the whole design,construction,and operation *** methods for evaluating adhesion behavior are summarized,including macroscopic adhesion performance tests,image analysis technology,and model *** is not objective to evaluate the aggregate adhesion behavior of chip seal only by a single evaluation method.A comprehensive evaluation based on the micro-macro multi-scale method should be considered in the future.

关键词： Chip seal Adhesion behavior Asphalt binder Aggregate

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Early Triassic Volcanic Rocks in the Western Yarlung Zangbo Suture Zone:Implications for the Opening of the Neo-Tethys Ocean

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 324-336页

作者： HE Juan LI Yalin HOU Yunling zhou Aorigele wei Yushuai CHEN Xi DAI Jingen School of Civil Engineering and Architecture West Yunnan University of Applied SciencesDaliYunnan 671006China School of Earth sciences and Resources China University of Geosciences(Beijing)Beijing 100080China West Yunnan University of Applied sciences DaliYunnan 671006China MLR Key Laboratory of Metallogeny and Mineral Assessment Institute of Mineral ResourcesChinese Academy of Geological SciencesBeijing 100080China

In this study,zircon U-Pb dating of volcanic rocks from the Zhongba ophiolite of the Yarlung Zangbo Suture Zone(YZSZ)in southern Xizang(Tibet)yielded an age of 24.±3 *** to whole rock geochemical and Sr-NdPb isotopic data,the Early Triassic samples could be divided into two groups:Group 1 with P-MORB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70253–0.70602,ε_(Nd)(t)values of 4.2–5.3,(^(206)Pb/^(204.Pb)_(t)ratios of 16.353–18.222,(^(207)Pb/^(204.Pb)_(t)ratios of 15.4.4.15.564.and(^(208)Pb/^(204.Pb)_(t)ratios of 35.665–38.136;Group 2 with OIB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.7024.–0.70513,ε_(Nd)(t)values of 4.4.4.9,(^(206)Pb/^(204.Pb)_(t)ratios of 17.14.–18.328,(^(207)Pb/^(204.Pb)_(t)ratios of 15.4.1–15.575,and(^(208)Pb/^(204.Pb)_(t)ratios of 36.051–*** 2 rocks formed by partial melting of the mantle source enriched by a former plume,and assimilated continental crustal material during melt *** formation of Group 1 rocks corresponds to the mixing of OIB melts,with the same components as Group 2 and *** Zhongba Early Triassic rocks belong to the continental margin type ophiolite and formed in the continental–oceanic transition zone during the initial opening of the Neo-Tethys in southern Xizang(Tibet).

关键词： rift Early Triassic magmatism Yarlung Zangbo Suture Zone Neo-Tethys Southern Xizang Tibet

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Structural Dependence Learning Based on Self-attention for Face Alignment

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Machine Intelligence Research 2024年第3期21卷 514-525页

作者： Biying Li Zhiwei Liu wei zhou Haiyun Guo Xin Wen Min Huang Jinqiao Wang Foundation Model Research Center Institute of AutomationChinese Academy of SciencesBeijing100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing100083China Alpha(beijing)Private Equity Beijing100083China School of Computer Science National University of Defense TechnologyChangsha410073China

Self-attention aggregates similar feature information to enhance the features. However, the attention covers nonface areas in face alignment, which may be disturbed in challenging cases, such as occlusions, and fails to predict landmarks. In addition, the learned feature similarity variance is not large enough in the experiment. To this end, we propose structural dependence learning based on self-attention for face alignment (SSFA). It limits the self-attention learning to the facial range and adaptively builds the significant landmark structure dependency. Compared with other state-of-the-art methods, SSFA effectively improves the performance on several standard facial landmark detection benchmarks and adapts more in challenging cases.

关键词： Computer vision face alignment self-attention facial structure contextual information

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Enhancing cellular behavior in repaired tissue via silk fibroin-integrated triboelectric nanogenerators

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Microsystems & Nanoengineering 2024年第3期10卷 137-147页

作者： Zhelin Li Shuxing Xu Zijie Xu Sheng Shu Guanlin Liu Jianda zhou Ding Lin wei Tang Changsha Aier Eye Hospital Aier School of OphthalmologyCentral South UniversityChangshaHunanChina The Xiangya Hospital Central South UniversityChangshaHunanChina beijing Institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China Center on Nanoenergy Research School of Physical Science&TechnologyGuangxi UniversityNanning 530004China School of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China Department of Plastic Surgery the Third Xiangya HospitalChangshaHunanChina

Triboelectric nanogenerators(TENGs)have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic *** their potential benefits,the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and ***,further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical *** this study,we present a flexible silk fibroin-based triboelectric nanogenerator(SFB-TENG)that features an on-skin substrate and is characterized by excellent skin compliance and air/water *** range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926,NIH-3T3 and RSC96 ***,apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 *** addition,the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 *** research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design,as well as its safe operating conditions for use in biomedical *** findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration.

关键词： overcome spite generating

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Optimizing high-coordination shell of Co-based single-atom catalysts for efficient ORR and zinc-air batteries

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Journal of Energy Chemistry 2024年第8期95卷 306-314,I0007页

作者： Yugang Qi Qing Liang Kexin Song Xinyan zhou Meiqi Liu Wenwen Li Fuxi Liu zhou Jiang Xu Zou Zhongjun Chen wei Zhang weitao Zheng Key Laboratory of Automobile Materials MOE School of Materials Science&Engineering Electron Microscopy Centerand International Center of Future ScienceJilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy MaterialsJilin UniversityChangchun 130012JilinChina Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China

Atom-level modulation of the coordination environment for single-atom catalysts(SACs)is considered as an effective strategy for elevating the catalytic *** the MNxsite,breaking the symmetrical geometry and charge distribution by introducing relatively weak electronegative atoms into the first/second shell is an efficient way,but it remains challenging for elucidating the underlying mechanism of ***,a practical strategy was reported to rationally design single cobalt atoms coordinated with both phosphorus and nitrogen atoms in a hierarchically porous carbon derived from metal-organic frameworks.X-ray absorption spectrum reveals that atomically dispersed Co sites are coordinated with four N atoms in the first shell and varying numbers of P atoms in the second shell(denoted as Co-N/P-C).The prepared catalyst exhibits excellent oxygen reduction reaction(ORR)activity as well as zinc-air battery *** introduction of P atoms in the Co-SACs weakens the interaction between Co and N,significantly promoting the adsorption process of ^(*)OOH,resulting in the acceleration of reaction kinetics and reduction of thermodynamic barrier,responsible for the increased intrinsic *** discovery provides insights into an ultimate design of single-atom catalysts with adjustable electrocatalytic activities for efficient electrochemical energy conversion.

关键词： Electrocatalytic Oxygen reduction reaction Single atom catalyst Shell coordination optimization

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Micromechanism and mathematical model of stress sensitivity in tight reservoirs of binary granular medium

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Petroleum Science 2024年第3期21卷 1780-1795页

作者： Jian-Bang Wu Sheng-Lai Yang Qiang Li Kun Yang Can Huang Dao-Ping Lv wei zhou State Key Laboratory of Petroleum Resources and Engineering China University of Petroleum(Beijing)Beijing2249China Laboratoire de G eologie Ecole Normale Sup erieure/CNRS UMR8538PSL Research UniversityParis75005France Research Institute of Exploration and Development Xinjiang Oilfield CompanyKaramay834000XinjiangChina

Research on reservoir rock stress sensitivity has traditionally focused on unary granular structures,neglecting the binary nature of real reservoirs,especially tight *** the stresssensitive behavior and mathematical characterization of binary granular media remains a challenging *** this study,we conducted online-NMR experiments to investigate the permeability and porosity evolution as well as stress-sensitive control mechanisms in tight sandy conglomerate *** results revealed stress sensitivity coefficients between 0.04. and 0.098 and permeability damage rates ranging from 65.6%to 90.9%,with an average pore compression coefficient of 0.0168—0.0208 MPa ***-scale compression occurred in three stages:filling,compression,and compaction,with matrix pores playing a dominant role in pore *** stress sensitivity of binary granular media was found to be influenced by the support structure and particle *** stress sensitivity was associated with small fine particle size,high fines content,high uniformity coefficient of particle size,high plastic deformation,and low Young's ***-supported samples exhibited a high irreversible permeability damage rate(average=74.2%)and stress sensitivity coefficients(average=0.089),with pore spaces more *** contrast,grain-supported samples showed low stress sensitivity coefficients(average=0.021)at high stress *** on the experiments,we developed a mathematical model for stress sensitivity in binary granular media,considering binary granular properties and nested interactions using Hertz contact deformation and Poiseuille *** describing the change in activity content of fines under stress,we characterized the non-stationary state of compressive deformation in the binary granular structure and classified the reservoir into three *** model was applied for production prediction using actual data from the Mahu reservoir in China,showing that the e

关键词： Stress sensitivity Binary granular medium Tight reservoir Online-NMR Reservoir energy retention rate

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Flurbiprofen microneedle patches for the management of acute postoperative pain

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Nano Research 2024年第8期17卷 7493-7503页

作者： Huaqing Chu Yanyan Zhang Yuan Yang Jiangtao Xue Cong Li wei Zhang zhou Li Hui Zheng national Cancer Center/national Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China beijing Institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China Key Laboratory of Hunan Province for Integrated Traditional chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases School of Integrated Chinese and Western MedicineHunan University of Chinese MedicineChangsha 410208China School of Life Science Institute of Engineering MedicineBeijing Institute of TechnologyBeijing 100081China Institute of Process Engineering Chinese Academy of SciencesBeijing 100190China

Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are *** study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be *** crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic *** solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared *** demonstrated increasing mechanical strength with higher *** release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of *** vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 *** tests confirmed good ***/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.

关键词： microneedle postoperative pain flurbiprofen non-steroid anti-inflammatory drug cross-linked gelatin

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