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World Journal of Gastroenterology 2024年第8期30卷 843-854页

作者： Hong-xiao Wu xiao-Yan Ding Ya-Wen Xu Ming-Hua Yu xiao-Mi Li na Deng Jing-Long chen Cancer Center Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

BACKGROUND Hepatocellular carcinoma(HCC)patients complicated with portal vein tumor thrombus(PVTT)exhibit poor prognoses and treatment responses.AIM To investigate efficacies and safety of the combination of PD-1 inhibitor,transcatheter arterial chemoembolization(TACE)and Lenvatinib in HCC subjects comorbid with PVTT.METHODS From January 2019 to December 2020,HCC patients with PVTT types Ⅰ-Ⅳ were retrospectively enrolled at Beijing Ditan Hospital.They were distributed to either the PTL or TACE/Lenvatinib(TL)group.The median progression-free survival(mPFS)was set as the primary endpoint,while parameters like median overall survival,objective response rate,disease control rate(DCR),and toxicity level served as secondary endpoints.RESULTS Forty-one eligible patients were finally recruited for this study and divided into the PTL(n=18)and TL(n=23)groups.For a median follow-up of 21.8 months,the DCRs were 88.9%and 60.9%in the PTL and TL groups(P=0.046),res-pectively.Moreover,mPFS indicated significant improvement(HR=0.25;P<0.001)in PTL-treated patients(5.4 months)compared to TL-treated(2.7 months)patients.There were no treatment-related deaths or differences in adverse events in either group.CONCLUSION A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types Ⅰ-Ⅳ.

关键词： Hepatocellular carcinoma Transcatheter arterial chemoembolization Lenvatinib PD-1 inhibitor Portal vein tumor thrombus

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

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Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： Yan Sun Xiu-na Yang Shuang-Shuang Yang Yi-Zhu Lyu Bing Zhang Kai-Wen Liu na Li Jia-chen Cui Guang-Xiang Huang cheng-Lin Liu Jie Xu Jian-Qing Mi Zhu chen xiao-Hu Fan Sai-Juan chen Shuo chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China national Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular membrane.However,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based therapies.We co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple myeloma.Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity.Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution.BCMA-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived cells.Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated

Mechanism of Mingjing Granules in Treating Wet Age-Related Macular Degeneration Based on Network Pharmacology and Experimental Verification

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 22-32页

作者： xiao-Yu Li Li-na Liang Wei-Jun Zhang Yun Gao Qiang chen Eye Function Laboratory Eye HospitalChina Academy of Chinese Medical SciencesBeijingChina China Evidence-Based Medicine Center for Traditional Chinese Medicine BeijingChina Center for East-West Medicine UCLA David Geffen School of MedicineLos AngelesCAUSA

Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and to provide a new reference for the currently limited treatment of wAMD.Materials and Methods:We searched TCMSP,GeneCards,OMIM,PharmGkb,TTD,and DrugBank database to screen the main active ingredients of Mingjing granules and their therapeutic targets of wAMD.The network of active components and targets was constructed using Cytoscape3.6.1 software,which was also used for the topological analysis of target genes.The network of Protein-Protein Interactions(PPI)was mapped using the String platform.We also used R language to do the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway for additional analysis.Molecular docking studies were finished by Chemoffice,Autodock,and Pymol.Finally,the efficacy of the Mingjing granules was examined in animal experiments,in which we used enzyme-linked immunosorbent assay to the contents of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9)levels in peripheral blood.Results:Active compounds,including quercetin,lignocaine,and kaempferol,were found.PPI network analysis showed that tumor necrosis factor(TNF),MMP-9,epidermal growth factor(EGF),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase-3(CASP3)were related to both Mingjing granules and wAMD.GO and KEGG pathway analysis showed that these targets were mainly involving lipids and atherosclerosis,TNF,and interleukin-17(IL-17)signaling pathways.Docking studies suggested that quercetin and luteolin can fit in the binding pocket of four target proteins(CASP3,EGF,PTGS2,and TNF).In the vivo experiment,the Mingjing granules were found to be effective on the expression of VEGF and MMP-9 in peripheral blood.Conclusions:This study initially reveals the multi-constituent,multi-target,and multi-pathway mechanism of action of Mingjing granules in the treatment of wAMD and impli

关键词： Experimental verification Mingjing granules molecular docking network pharmacology wet age-related macular degeneration

The infection kinetics and transmission potential of two Guaico Culex viruses in Culex quinquefasciatus mosquitoes

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Virologica Sinica 2024年第2期39卷 228-234页

作者： Ru-Yi chen Teng Zhao Jing-Jing Guo Feng Zhu na-na Zhang xiao-Feng Li Hai-Tao Liu Fei Wang Yong-Qiang Deng cheng-Feng Qin College of Bioscience and Bioengineering Jiangxi Agricultural UniversityNanchang330045China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMSBeijing100071China School of Life Sciences Southwest Forestry UniversityKunming650224China

Guaico Culex virus(GCXV)is a newly identified segmented Jingmenvirus from Culex spp.mosquitoes in Central and South America.The genome of GCXV is composed of four or five single-stranded positive Rna segments.However,the infection kinetics and transmission capability of GCXV in mosquitoes remain unknown.In this study,we used reverse genetics to rescue two GCXVs(4S and 5S)that contained four and five Rna segments,respectively,in C6/36 cells.Further in vitro characterization revealed that the two GCXVs exhibited comparable replication kinetics,protein expression and viral titers.Importantly,GCXV Rnas were detected in the bodies,salivary glands,midguts and ovaries of Culex quinquefasciatus at 4–10 days after oral infection.In addition,two GCXVs can colonize Cx.quinquefasciatus eggs,resulting in positive rates of 15%–35%for the second gonotrophic cycle.In conclusion,our results demonstrated that GCXVs with four or five Rna segments can be detected in Cx.quinquefasciatus eggs during the first and second gonotrophic cycles after oral infection.

关键词： Guaico Culex virus(GCXV) Jingmenvirus Culex quinquefasciatus Vertical transmission

Isotopic characteristics and source analysis of atmospheric ammonia during agricultural periods in the Xichuan area of the Danjiangkou Reservoir

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Journal of Environmental Sciences 2024年第2期136卷 460-469页

作者： xiaoshu chen Tongqian Zhao Chunyan xiao xiaoming Guo Feihong chen Institute of Resources and Environment Henan Polytechnic UniversityJiaozuo 454000China

Nitrogen deposition is an important means of exogenous nitrogen input in reservoir water.Agricultural activities around the reservoir lead to a sharp increase in the concentration of ammonia in the atmosphere,which poses a threat to the reservoir water body.Clarifying the contribution of agricultural ammonia release to atmospheric NH_(x)(gaseous NH_(3)and particulate NH_(4)^(+)),in the reservoir area can provide a theoretical foundation for local reactive nitrogen control.We collected atmospheric NH_(3)and NH_(4)^(+)samples during the agricultural periods and analyzed the isotopic characteristics of atmospheric NH_(x)and the contribution rates of different ammonia sources in the Xichuan area of the Danjiangkou Reservoir.The results showed that the initialδ~(15)N values of NH_(3)(-30.0‰to–7.2‰)and particulate NH_(4)^(+)(–33‰to+4.9‰for finer and coarser particles,respectively)are different,and their contribution ratios from dissimilar ammonia sources are also different,among which NH_(4)^(+)is more susceptible to meteorological factors.However,since the atmospheric NH_(x)in the Xichuan area is mainly gaseous NH_(3),the final sources of atmospheric ammonia nitrogen source depend on gaseous NH_(3).Agricultural sources(59%-74%)were the main NH_(3)sources in this area.Among them,the fertilizer use emission was dominant;it had the highest contribution rate in summer during the agricultural period and a more prominent impact in areas with less human interference.Reasonable regulation of the application of high-ammonia releasing fertilizer,especially during the agricultural period in summer,is an effective way to reduce the threat of atmospheric ammonia to water health.

关键词： Danjiangkou reservoir Atmospheric ammonia nitrogen Isotope Ammonia source analysis Agricultural sources

Bioinspired nanomaterials for wearable sensing and human–machine interfacing

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nano Research 2024年第2期17卷 445-461页

作者： Vishesh Kashyap Junyi Yin xiao xiao Jun chen Department of Bioengineering University of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Mechanical and Aerospace Engineering University of CaliforniaLos AngelesLos AngelesCA 90095USA

The inculcation of bioinspiration in sensing and human–machine interface(HMI)technologies can lead to distinctive characteristics such as conformability,low power consumption,high sensitivity,and unique properties like self-healing,self-cleaning,and adaptability.Both sensing and HMI are fields rife with opportunities for the application of bioinspired nanomaterials,particularly when it comes to wearable sensory systems where biocompatibility is an additional requirement.This review discusses recent development in bioinspired nanomaterials for wearable sensing and HMIs,with a specific focus on state-of-the-art bioinspired capacitive sensors,piezoresistive sensors,piezoelectric sensors,triboelectric sensors,magnetoelastic sensors,and electrochemical sensors.We also present a comprehensive overview of the challenges that have hindered the scientific advancement in academia and commercialization in the industry.

关键词： bioinspired nanomaterials human–machine interface wearable sensors wearable bioelectronics

Neuronomodulation of Excitable Neurons

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Neuroscience Bulletin 2024年第1期40卷 103-112页

作者： Yizhang chen Lin xiao Jian Qiu Institute of Neuroscience Second Military Medical UniversityShanghai 200433China Institute for Brain Research and Rehabilitation Key Laboratory of BrainCognition and Education Sciences of Ministry of EducationSouth China Normal UniversityGuangzhou 510631China Department of Chemical Physiology and Biochemistry Oregon Health and Science UniversityPortlandOR 97239USA

Neuronomodulation refers to the modulation of neural conduction and synaptic transmission(i.e.,the conduction process involved in synaptic transmission)of excitable neurons via changes in the membrane potential in response to chemical substances,from spillover neuro-transmitters to paracrine or endocrine hormones circulating in the blood.Neuronomodulation can be direct or indirect,depending on the transduction pathways from the ligand binding site to the ion pore,either on the same molecule,i.***.the ion channel,or through an intermediate step on different molecules.The major players in direct neurono-modulation are ligand-gated or voltage-gated ion channels.The key process of direct neuronomodulation is the binding and chemoactivation of ligand-gated or voltage-gated ion channels,either orthosterically or allosterically,by various ligands.Indirect neuronomodulation involves metabotropic receptor-mediated slow potentials,where steroid hormones,cytokines,and chemokines can implement these actions.Elucidating neuronomodulation is of great significance for understanding the physiological mechanisms of brain function,and the occurrence and treatment of diseases.

关键词： Neuron Membrane potential Excitability Chemoactivation Neuronomodulation

A Fluctuation Test for Structural Change Detection in Heterogeneous Panel Data Models

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Journal of Systems Science & Complexity 2024年第3期37卷 1184-1208页

作者： LI Fuxiao xiao Yanting chen Zhanshou Department of Applied Mathematics Xi'an University of TechnologyXi'an 710048China School of Mathematics and Statistics Qinghai Normal UniversityXining 810008China Academy of Plateau Science and Sustainability Xining 810008China

Structural change in panel data is a widespread phenomena. This paper proposes a fluctuation test to detect a structural change at an unknown date in heterogeneous panel data models with or without common correlated effects. The asymptotic properties of the fluctuation statistics in two cases are developed under the null and local alternative hypothesis. Furthermore, the consistency of the change point estimator is proven. Monte Carlo simulation shows that the fluctuation test can control the probability of type I error in most cases, and the empirical power is high in case of small and moderate sample sizes. An application of the procedure to a real data is presented.

关键词： Common correlated effects fuctuation test heterogeneous panel data models structural change detection

Reactive Transport Process of Earthquake-induced Hydrochemical Changes in Guanding Thermal Spring,Western Sichuan,China

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Acta Geologica Sinica(English Edition) 2024年第1期98卷 241-249页

作者： na Jin JIANG Xue SHI Zheming chen Yanmei Hubei Key Laboratory of Petroleum Geochemistry and Environment(Yangtze University) Wuhan 430100China School of Environmental Studies China University of GeosciencesWuhan 430074China School of Water Resources and Environment China University of GeosciencesBeijing 100083China State Key Laboratory of Water Resource Protection and Utilization in Coal Mining Beijing 100000China

Earthquake-related hydrochemical changes in thermal springs have been widely observed;however,quantitative modeling of the reactive transport process is absent.In the present study,we apply reactive transport simulation to capture the hydrochemical responses in a thermal spring following the Wenchuan Ms 8.0 and Lushan Ms 7.0 earthquakes.We first constrain deep reservoir geothermal fluid compositions and temperature by multicomponent geothermometry,and then a reactive geochemical transport model is constructed to reproduce the hydrochemical evolution process.The results show that the recharge from the shallow aquifer increases gradually until it reaches a peak because of the permeability enhancement caused by the Lushan earthquake,which may be the mechanism to explain the earthquake-related hydrochemical responses.In contrast to the postseismic effect of the Wenchuan earthquake,the chemical evolution can be considered as hydrochemical anomalies related to the Lushan earthquake.This study proves that the efficient simulation of reactive transport processes is useful for investigating earthquake-related signals in hydrochemical time series.

关键词： earthquake hydrochemical changes reactive geochemical transport model Kangding area

Global Phase Portraits of Uniform Isochronous Centers System of Degree Six with Polynomial Commutator

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 577-599页

作者： Li-na GUO Ai-yong chen Shuai-feng ZHAO School of Mathematics and Statistics Henan University of Science and TechnologyLuoyang 471023China Department of Mathematics Hunan First Normal UniversityChangsha 410205China School of Mechatronics Engineering Henan University of Science and TechnologyLuoyang 471023China

This paper studies the global phase portraits of uniform isochronous centers system of degree six with polynomial commutator.Such systems have the form x=-y+xf(x,y),y=x+yf(x,y),where f(x,y)=a_(1)x+a_(2)xy+a_(3)xy^(2)+a_(4)xy^(3)+a_(5)xy^(4)=xσ(y),and any zero of 1+a_(1)y+a_(2)y^(2)+a_(3)y^(3)+a_(4)y^(4)+a_(5)y^(5),y=y is an invariant straight line.At last,all global phase portraits are drawn on the Poincare disk.

关键词： global phase portraits uniform isochronous center polynomial commutator invariant straight lines