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NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

Current Medical Science 2024年第1期44卷 168-179页

作者： Wei XUE Ting WANG Wen-jing TIAN Si-qi PANG hua-feng zhang Wei-dong JIA Department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

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Exploring the Cation Regulation Mechanism for Interfacial Water Involved in the Hydrogen Evolution Reaction by In Situ Raman Spectroscopy

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Nano-Micro Letters 2024年第3期16卷 303-312页

作者： Xueqiu You Dongao zhang Xia‑Guang zhang Xiangyu Li Jing‑hua Tian Yao‑Hui Wang Jian‑feng Li School of Ocean Information Engineering Fujian Provincial Key Laboratory of Oceanic Information Perception and Intelligent ProcessingJimei UniversityXiamen 361021People’s Republic of China State Key Laboratory of Physical Chemistry of Solid Surfaces MOE Key Laboratory of Spectrochemical Analysis and InstrumentationiChEMCollege of Chemistry and Chemical EngineeringCollege of MaterialsCollege of EnergyXiamen UniversityXiamen 361005People’s Republic of China Key Laboratory of Green Chemical Media and Reactions Ministry of EducationCollaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsCollege of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007People’s Republic of China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005People’s Republic of China

Interfacial water molecules are the most important participants in the hydrogen evolution reaction(HER).Hence,understanding the behavior and role that interfacial water plays will ultimately reveal the HER mechanism.Unfortunately,investigating interfacial water is extremely challenging owing to the interference caused by bulk water molecules and complexity of the interfacial environment.Here,the behaviors of interfacial water in different cationic electrolytes on Pd surfaces were investigated by the electrochemistry,in situ core-shell nanostructure enhanced Raman spectroscopy and theoretical simulation techniques.Direct spectral evidence reveals a red shift in the frequency and a decrease in the intensity of interfacial water as the potential is shifted in the positively direction.When comparing the different cation electrolyte systems at a given potential,the frequency of the interfacial water peak increases in the specified order:Li+

关键词： In situ Raman Interfacial water Hydrogen evolution reaction Cations

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Mechanism of local solidification time variations with melt rate during vacuum arc remelting process of 8Cr4Mo4V high-strength steel

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Journal of Iron and Steel Research(International) 2024年第2期31卷 377-388页

作者： Tao Pan Hong-chun Zhu Zhou-hua Jiang hua-bing Li Rui zhang Hao feng School of Metallurgy Northeastern UniversityShenyang110819LiaoningChina State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang110819LiaoningChina

A 2D axisymmetric numerical model was established to investigate the variations of molten pool with different melt rates during the vacuum arc remelting of 8Cr4Mo4V high-strength steel,and the ingot growth was simulated by dynamic mesh techniques.The results show that as the ingot grows,the molten pool profile changes from shallow and flat to V-shaped,and both the molten pool depth and the mushy width increase.Meanwhile,the variation of both the molten pool shape and the mushy width melt rate is clarified by the thermal equilibrium analysis.As melt rate increases,both the molten pool depth and the mushy width increase.It is caused by the increment in sensible heat stored in the ingot due to the limitation of the cooling capacity of the mold.The nonlinear increment in sensible heat leads to a nonlinear increase in the mushy width.In addition,as melt rate increases,the local solidification time(LST)of ingot decreases obviously at first and then increases.When melt rate is controlled in a suitable range,LST is the lowest and the secondary dendrite arm spacing of the ingot is the smallest,which can effectively improve the compactness degree of 8Cr4Mo4V high-strength steel.

关键词： 8Cr4Mo4V high-strength steel Vacuum arc remelting process Melt rate Molten pool Local solidification time

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Cr-catalyzed allylic C(sp^(3))–H addition to aldehydes enabled by photoinduced ligand-to-metal charge transfer

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Science China Chemistry 2024年第5期67卷 1589-1595页

作者： Xianrong Zeng feng-hua zhang Runchen Lai Xiaoyu Lin Zhaobin Wang Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province Department of ChemistrySchool of Science and Research Center for Industries of the FutureWestlake UniversityHangzhou 310030China Institute of Natural Sciences Westlake Institute for Advanced StudyHangzhou 310024China Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province Instrumentation and Service Center for Molecular SciencesWestlake UniversityHangzhou 310024China

Photoinduced ligand-to-metal charge transfer(LMCT) has emerged as an effective strategy for synthesizing organic molecules in a sustainable manner. However, the majority of existing reports on selective C(sp^(3))–H bond functionalization via photoinduced LMCT focus on the use of late transition metals or rare-earth metals for radical additions or cross-couplings. In contrast, the utilization of photoinduced LMCT with 3d early transition metals poses a significant challenge. Herein, we describe an unprecedented approach to allylic C(sp^(3))–H addition to aldehydes, employing chromium(Cr) complexes as catalysts through visible-light-induced LMCT. By investigating the reaction pathway through various mechanistic studies, including radical trapping, kinetic isotope effect(KIE) analysis, and transient absorption spectroscopy, valuable insights have been gained. The proposed mechanism suggests the intermediacy of bromine radicals through homolysis of the Cr–Br bond. Notably, this protocol expands our understanding of the photochemical properties of earth-abundant Cr complexes.

关键词： Cr catalysis photoinduced ligand-to-metal charge transfer hydrogen-atom transfer carbonyl addition

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Counteracting effects on ENSO induced by ocean chlorophyll interannual variability and tropical instability wave-scale perturbations in the tropical Pacific

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Science China Earth Sciences 2024年第2期67卷 387-404页

作者： Rong-hua zhang feng TIAN Qidong SHI Xiujun WANG Tongwen WU School of Marine Sciences Nanjing University of Information Science and TechnologyNanjing210044China Laoshan Laboratory Qingdao266237China Key Laboratory of Ocean Circulation and Waves Institute of OceanologyChinese Academy of SciencesQingdao266071China University of Chinese Academy of Sciences Beijing101408China Faculty of Geographical Sciences Beijing Normal UniversityBeijing100875China Earth System Modeling and Prediction Centre China Meteorological AdministrationBeijing100081China

Large perturbations in chlorophyll(Chl)are observed to coexist at interannual and tropical instability wave(TIW)scales in the tropical Pacific;at present,their combined effects on El Ni?o-Southern Oscillation(ENSO)through ocean biologyinduced heating(OBH)feedbacks are not understood well.Here,a hybrid coupled model(HCM)for the atmosphere and ocean physics-biogeochemistry(AOPB)in the tropical Pacific is adopted to quantify how ENSO can be modulated by Chl perturbations at interannual and TIW scales,individually or collectively,respectively.The HCM-based sensitivity experiments demonstrate a counteracting effect on ENSO:the bio-climate feedback due to large-scale Chl interannual variability acts to damp ENSO through its impact on upper-ocean stratification and vertical mixing,whereas that due to TIW-scale Chl perturbations tends to amplify ENSO.Because ENSO simulations are sensitively dependent on the ways Chl effects are represented at these different scales,it is necessary to adequately take into account these related differential Chl effects in climate modeling.A bias source for ENSO simulations is illustrated that is related with the Chl effects in the tropical Pacific,adding in a new insight into interactions between the climate system and ocean ecosystem on different scales in the region.These results reveal a level of complexity of ENSO modulations resulting from Chl effects at interannual and TIW scales,which are associated with ocean biogeochemical processes and their interactions with physical processes in the tropical Pacific.

关键词： Ocean chlorophyll Bio-climate feedbacks Interannual variability Tropical instability waves Counteracting effects A hybrid coupled model

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Microneedle patch loaded with ferritin-nanocaged doxorubicin for locally targeted drug delivery and efficient skin cancer treatment

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Particuology 2024年第5期88卷 282-289页

作者： feng Li Yuan Yang hua Yue Shuang Wang Xiao zhang Wei Wei State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190China Key Laboratory of Biopharmaceutical Preparation and Delivery Chinese Academy of SciencesBeijing100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China

Ferritin has emerged as a promising nanocarrier for delivering therapeutic agents to tumours.However,the limited drug loading and the off-target impacts after systemic administration remain challenges for cancer treatment with ferritin-based agents.Herein,we develop a microneedle patch loaded with ferritin-nanocaged doxorubicin(DoxFe@Fn/MN)for skin cancer treatment.Briefly,doxorubicin(Dox)is encapsulated in ferritin(Fn)using an iron core-assisted strategy,which results in a 3.4-fold increase in Dox loading compared to the direct loading method.Then,a polyvinyl alcohol-based microneedle(MN)patch is used for the transdermal delivery of DoxFe@Fn,enabling targeted tumour accumulation of DoxFe@Fn and preventing off-target impacts.The released DoxFe@Fn can bind to CD71 highly expressed on skin cancer cells,facilitating its uptake.As a result,the DoxFe@Fn/MN therapy presents a robust antitumour effect in a melanoma tumour model,showing its potential as a promising therapeutic modality for skin cancer treatment.

关键词： Ferritin Microneedle Skin cancer Drug delivery

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Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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Research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao zhang Yupeng Cun Weixiang Chen Yang Yang Qian zhang huanhuan Li Jun Zhong Xuyang zhang hua feng Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(NPCs)has been shown to be an effective treatment for ischemic stroke.However,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia.Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic stroke.However,the role of ASIC1a in NPCs post-ischemia remains elusive.Here,our results indicated that ASIC1a was expressed in NPCs with channel functionality,which could be activated by extracellular acidification.Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of ASIC1a.In vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

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Recent progress of Pt-based oxygen reduction reaction catalysts for proton exchange membrane fuel cells

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Rare Metals 2024年第6期43卷 2444-2468页

作者： feng Zhan Kun-Song Hu Jin-hua Mai Li-Sheng zhang Zhen-Guo zhang huan He Xin-hua Liu School of Resources Environment and MaterialsGuangxi University School of Transportation Science and Engineering Beihang University IDTECH (Suzhou) Co.Ltd Dyson School of Design Engineering Imperial College London

With the increasing consumption of fossil fuels,proton exchange membrane fuel cells(PEMFCs) have attracted considerable attention as green and sustainable energy conversion devices.The slow kinetics of the cathodic oxygen reduction reaction(ORR) has a major impact on the performance of PEMFCs,and although platinum(Pt) can accelerate the reaction rate of the ORR,the scarcity and high cost of Pt resources still limit the development of PEMFCs.Therefore,the development of low-cost high-performance ORR catalysts is essential for the commercial application and development of PEMFCs.This paper reviews the research progress of researchers on Pt-based ORR catalysts in recent years,including Pt/C catalysts,Pt-based alloy catalysts,Pt-based intermetallic compounds,and Pt-based single-atom catalysts(SACs),with a focus on Pt-based alloy catalysts with different nanostructures.We described in detail the difficulties and solutions in the research process of various ORR catalysts and explained the principle of their activity enhancement with density functional theory(DFT).In addition,an outlook on the development of Pt-based catalysts is given,and reducing the amount of Pt used and improving the performance of catalysts are the directions to work on in the coming period.

关键词： Pt-based catalysts PEMFCs Pt-based intermetallic compounds Single-atom catalysts

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Heteroepitaxial growth of Au@Pd core–shell nanocrystals with intrinsic chiral surfaces for enantiomeric recognition

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Rare Metals 2024年第1期43卷 225-235页

作者： feng-Xia Wu feng-hua Li Xia-Li Lv Qi-Xian zhang Guo-Bao Xu Wen-Xin Niu State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Shaoxing Institute of Technology Shanghai UniversityShaoxing 312000China University of Science and Technology of China Hefei 230026China School of Materials Science and Engineering Shanghai UniversityShanghai 200436China Zhejiang Institute of Advanced Materials Shanghai UniversityJiashan 314113China University of Chinese Academy of Sciences Beijing 100039China

Noble metal surfaces with intrinsic chirality serve as an ideal candidate for investigating enantioselective chemistry due to their superior chemical durability and high catalytic activity.Recently,significant advance has been made in synthesizing metal nanocrystals with intrinsic chirality.Nonetheless,the majority reports are limited to gold.Herein,through a heteroepitaxial growth strategy,the synthesis of metal nanocrystals with intrinsic chirality to palladium was extended for the first time and their application in enantioselective recognition was demonstrated.The heteroepitaxial growth strategy allows for transferring the chirality of homochiral Au nanocrystals to Au@Pd core–shell nanocrystals.By employing the chiral Au@Pd nanocrystals as enantiomeric recognizing elements,a series of electrochemical sensors for chiral discrimination were developed.Under optimal conditions,the peak potential between D-dihydroxyphenylalanine(D-DOPA)and L-dihydroxyphenylalanine(L-DOPA)is about 80 m V,and the peak current of D-DOPA is 2 times as much as that of L-DOPA,which enables the determination of the enantiomeric excess(EE,%)of L-DOPA.Overall,this report not only introduces a heteroepitaxial growth strategy to synthesize metal nanocrystals with intrinsic chirality,but also demonstrates the superior capability of integrating intrinsic chirality and catalytic properties into metal nanocrystals for chiral recognition.

关键词： Core–shell nanostructures Chirality transfer Electrochemical sensors Chiral recognition Chiroplasmonics

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On the Performances of Estimating Stellar Atmospheric Parameters from CSST Broad-band Photometry

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Research in Astronomy and Astrophysics 2024年第4期24卷 161-173页

作者： Rui-feng Shi Yang huang Xin-Yi Li hua-Wei zhang School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China South-Western Institute for Astronomy Research Yunnan UniversityKunming 650500China CAS Key Lab of Optical Astronomy Key Laboratory of Space Astronomy and TechnologyNational Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China College of Physics and Electronic Engineering Qilu Normal UniversityJinan 250200China Department of Astronomy School of PhysicsPeking UniversityBeijing 100871China Kavli Institute for Astronomy and Astrophysics Peking UniversityBeijing 100871China

Deriving atmospheric parameters of a large sample of stars is of vital importance to understand the formation and evolution of the Milky Way.Photometric surveys,especially those with near-ultraviolet filters,can offer accurate measurements of stellar parameters,with the precision comparable to that from low/medium resolution spectroscopy.In this study,we explore the capability of measuring stellar atmospheric parameters from Chinese Space Station Telescope(CSST)broad-band photometry(particularly in the near-ultraviolet bands),based on synthetic colors derived from model spectra.We find that colors from the optical and near-ultraviolet filter systems adopted by CSST show significant sensitivities to the stellar atmospheric parameters,especially the metallicity.According to our mock data tests,the precision of the photometric metallicity is quite high,with typical values of0.17 and 0.20 dex for dwarf and giant stars,respectively.The precision of the effective temperature estimated from broad-band colors are within 50 K.

关键词： methods:data analysis stars:abundances surveys

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