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Regulating metalloimmunology with nanomedicine for cancer therapy

Nano Research 2023年第12期16卷 13164-13181页

作者： Saibo Ma lin chen Muhammad Hamza Jing Chang Motao Zhu College of Marine Life Science Ocean University of ChinaQingdao 266003China CAS Key Laboratory for Biomedical Effects of Nanomaterials&Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266235China University of Chinese Academy of Sciences Beijing 100049China

Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by metals.Therefore,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating cancer.However,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting specificity.This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer.Essential trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune interplay.The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed.These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.

关键词： metalloimmunology metal metabolism cancer immunotherapy nano-enabled delivery system cGAS-STING pathway ferroptosis and cuprotosis

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High-entropy perovskite RETa_(3)O_(9) ceramics for high-temperature environmental/thermal barrier coatings

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Journal of Advanced Ceramics 2022年第4期11卷 556-569页

作者： lin chen Baihui LI Jun GUO Yuke ZHU Jing FENG Faculty of Material Science and Engineering Kunming University of Science and TechnologyKunming 650093China

Four high-entropy perovskite(HEP)RETa_(3)O_(9) samples were fabricated via a spark plasma sintering(SPS)method,and the corresponding thermophysical properties and underlying mechanisms were investigated for environmental/thermal barrier coating(E/TBC)applications.The prepared samples maintained low thermal conductivity(1.50 W·m^(−1)·K^(−1)),high hardness(10 GPa),and an appropriate Young’s modulus(180 GPa),while the fracture toughness increased to 2.5 MPa·m^(1/2).Nanoindentation results showed the HEP ceramics had excellent mechanical properties and good component homogeneity.We analysed the influence of different parameters(the disorder parameters of the electronegativity,ionic radius,and atomic mass,as well as the tolerance factor)of A-site atoms on the thermal conductivity.Enhanced thermal expansion coefficients,combined with a high melting point and extraordinary phase stability,expanded the applications of the HEP RETa_(3)O_(9).The results of this study had motivated a follow-up study on tantalate high-entropy ceramics with desirable properties.

关键词： high-entropy ceramics(HECs) tantalates thermal conductivity nanoindentation fracture toughness

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Functional characterization of piggyBac-like elements from Nilaparvata lugens(St?l)(Hemiptera:Delphacidae)

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第6期23卷 515-527页

作者： Jun LYU Qin SU Jinhui LIU lin chen Jiawei SUN Wenqing ZHANG State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

Piggy Bac is a transposable DNA element originally discovered in the cabbage looper moth(Trichoplusia ni).The T.ni piggyBac transposon can introduce exogenous fragments into a genome,constructing a transgenic organism.Nevertheless,the comprehensive analysis of endogenous piggyBac-like elements(PLEs)is important before using piggyBac,because they may influence the genetic stability of transgenic lines.Herein,we conducted a genome-wide analysis of PLEs in the brown planthopper(BPH)Nilaparvata lugens(St?l)(Hemiptera:Delphacidae),and identified a total of 28 PLE sequences.All N.lugens piggy Bac-like elements(NlPLEs)were present as multiple copies in the genome of BPH.Among the identified NlPLEs,NlPLE25 had the highest copy number and it was distributed on five chromosomes.The full length of NlPLE25 consisted of terminal inverted repeats and sub-terminal inverted repeats at both terminals,as well as a single open reading frame transposase encoding546 amino acids.Furthermore,NlPLE25 transposase caused precise excision and transposition in cultured insect cells and also restored the original TTAA target sequence after excision.A cross-recognition between the NlPLE25 transposon and the piggy Bac transposon was also revealed in this study.These findings provide useful information for the construction of transgenic insect lines.

关键词： Nilaparvata lugens piggyBac-like elements Transposon NlPLE25

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Nuclear transport proteins: structure, function, and disease relevance

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5657-5685页

作者： Yang Yang Lu Guo lin chen Bo Gong Da Jia Qingxiang Sun Department of Pulmonary and Critical Care Medicine Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduChina The Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengduChina Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of PediatricsWest China Second University HospitalState Key Laboratory of BiotherapySichuan UniversityChengduChina Department of Pathology State Key Laboratory of Biotherapy and Cancer CentreWest China HospitalSichuan Universityand Collaborative Innovation Centre of BiotherapyChengduChina

Proper subcellular localization is crucial for the functioning of biomacromolecules,including proteins and RNAs.Nuclear transport is a fundamental cellular process that regulates the localization of many macromolecules within the nuclear or cytoplasmic compartments.In humans,approximately 60 proteins are involved in nuclear transport,including nucleoporins that form membrane-embedded nuclear pore complexes,karyopherins that transport cargoes through these complexes,and Ran system proteins that ensure directed and rapid transport.Many of these nuclear transport proteins play additional and essential roles in mitosis,biomolecular condensation,and gene transcription.Dysregulation of nuclear transport is linked to major human diseases such as cancer,neurodegenerative diseases,and viral infections.Selinexor(KPT-330),an inhibitor targeting the nuclear export factor XPO1(also known as CRM1),was approved in 2019 to treat two types of blood cancers,and dozens of clinical trials of are ongoing.This review summarizes approximately three decades of research data in this field but focuses on the structure and function of individual nuclear transport proteins from recent studies,providing a cutting-edge and holistic view on the role of nuclear transport proteins in health and disease.In-depth knowledge of this rapidly evolving field has the potential to bring new insights into fundamental biology,pathogenic mechanisms,and therapeutic approaches.

关键词： complexes function structure

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Non-convex sparse optimization-based impact force identification with limited vibration measurements

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Frontiers of Mechanical Engineering 2023年第3期18卷 165-185页

作者： lin chen Yanan WANG Baijie QIAO Junjiang LIU Wei chenG Xuefeng chen National Key Laboratory of Aerospace Power System and Plasma Technology Xi'an Jiaotong UniversityXi'an 710049China School of Mechanical Engineering Xi'an Jiaotong UniversityXi'an 710049China

Impact force identification is important for structure health monitoring especially in applications involving composite structures.Different from the traditional direct measurement method,the impact force identification technique is more cost effective and feasible because it only requires a few sensors to capture the system response and infer the information about the applied forces.This technique enables the acquisition of impact locations and time histories of forces,aiding in the rapid assessment of potentially damaged areas and the extent of the damage.As a typical inverse problem,impact force reconstruction and localization is a challenging task,which has led to the development of numerous methods aimed at obtaining stable solutions.The classicalℓ2 regularization method often struggles to generate sparse solutions.When solving the under-determined problem,ℓ2 regularization often identifies false forces in non-loaded regions,interfering with the accurate identification of the true impact locations.The popularℓ1 sparse regularization,while promoting sparsity,underestimates the amplitude of impact forces,resulting in biased estimations.To alleviate such limitations,a novel non-convex sparse regularization method that uses the non-convexℓ1-2 penalty,which is the difference of theℓ1 andℓ2 norms,as a regularizer,is proposed in this paper.The principle of alternating direction method of multipliers(ADMM)is introduced to tackle the non-convex model by facilitating the decomposition of the complex original problem into easily solvable subproblems.The proposed method namedℓ1-2-ADMM is applied to solve the impact force identification problem with unknown force locations,which can realize simultaneous impact localization and time history reconstruction with an under-determined,sparse sensor configuration.Simulations and experiments are performed on a composite plate to verify the identification accuracy and robustness with respect to the noise of theℓ1-2-ADMM method.Results indicate that compared with other existing re

关键词： impact force identification inverse problem sparse regularization under-determined condition alternating direction method of multipliers

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Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 670-686页

作者： Ye Yang Wu Wen Feng-lin chen Ying-Jie Zhang Xiao-Cong Liu Xiao-Yan Yang Shan-Shan Hu Ye Jiang Jing Yuan Digestive Diseases Chengdu Qingbaijiang District People's HospitalChengdu 610300Sichuan ProvinceChina Digestive Diseases Chengdu Second People’s HospitalChengdu 610000Sichuan ProvinceChina Graduate School Chengdu Medical CollegeChengdu 610000Sichuan ProvinceChina

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were co

关键词： Pigment epithelium-derived factors Vascular endothelial growth factor Microvessel density Colorectal adenoma Colorectal cancer Targeted therapy

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Simultaneous manipulations of thermal expansion and conductivity in symbiotic ScTaO_(4)/SmTaO_(4) composites via multiscale effects

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先进陶瓷(英文) 2023年第8期12卷 1625-1640页

作者： lin chen Jiankun Wang Baihui Li Keren Luo Jing Feng Faculty of Materials Science and Engineering Kunming University of Science and TechnologyKunming 650093China

Effective manipulations of thermal expansion and conductivity are significant for improving operational performances of protective coatings,thermoelectric,and radiators.This work uncovers determinant mechanisms of the thermal expansion and conductivity of symbiotic ScTaO_(4)/SmTaO_(4) composites as thermal/environmental barrier coatings(T/EBCs),and we consider the effects of interface stress and thermal resistance.The weak bonding and interface stress among composite grains manipulate coefficient of thermal expansion(CTE)stretching from 6.4×10^(−6) to 10.7×10^(−6) K^(−1) at 1300℃,which gets close to that of substrates in T/EBC systems.The multiscale effects,including phonon scattering at the interface,mitigation of the phonon speed(vp),and lattice point defects,synergistically depress phonon thermal transports,and we estimate the proportions of different parts.The interface thermal resistance(R)reduces the thermal conductivity(k)by depressing phonon speed and scattering phonons because of different acoustic properties and weak bonding between symbiotic ScTaO_(4) and SmTaO_(4) ceramics in the composites.This study proves that CTE of tantalates can be artificially regulated to match those of different substrates to expand their applications,and the uncovered multiscale effects can be used to manipulate thermal transports of various materials.

关键词： thermal management coefficient of thermal expansion(CTE) interface thermal resistance(R) thermal stress(σ) thermal/environmental barrier coatings(T/EBCs)

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Mechanical property enhancements and amorphous thermal transports of ordered weberite-type RE_(3)Nb/TaO_(7) high-entropy oxides

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Journal of Advanced Ceramics 2023年第2期12卷 399-413页

作者： lin chen Keren LUO Baihui LI Mingyu HU Jing FENG Faculty of Materials Science and Engineering Kunming University of Science and TechnologyKunming 650093China Peking University Shenzhen Graduate School Shenzhen 518055China

A_(3)BO_(7)-type(A=rare earth(RE),B=Nb or Ta)oxides have been studied as protective coating materials because of their low thermal conductivity;however,their hardness,toughness,and stiffness are insufficient,particularly for members with webeirte-type structures.In this work,we have synthesized two high-entropy oxides(HEOs)of weberite-type RE niobates/tantalates(RE_(3)Nb/TaO_(7)),i.e.,(Nd_(1/7)Sm_(1/7)Eu_(1/7)Gd_(1/7)Dy_(1/7)Ho_(1/7)Er_(1/7))_(3)NbO_(7)(7HEOs-Nb)and(Nd_(1/7)Sm_(1/7)Eu_(1/7)Gd_(1/7)Dy_(1/7)Ho_(1/7)Er_(1/7))3(Nb_(1/2)Ta_(1/2))O_(7)(7HEOs-NbTa),to overcome the mechanical deficiencies.The short-and long-range ordered arrangements of RE cations in the A-site and Nb/Ta cations in the B-site were identified by the X-ray diffraction(XRD),scanning electron microscopy equipped with energy-dispersive spectrometry(EDS),and transmission electron microscopy.The enhancements in hardness(H=9.4 GPa)and fracture toughness(KIC=2.0 MPa·m^(1/2))were realized by grain refinement,solid solution strengthening,and high stiffness(K).The exceptional phase stability at 25-1500℃,amorphous thermal conductivity(k=1.5-1.7 W·m^(−1)·K^(−1) at 25-900℃),and high thermal expansion coefficients(TEC>11.0×10^(−6) K^(−1) at 1500℃)further supported their potential application as protective coating materials.

关键词： high-entropy oxides(HEOs) RE niobates/tantalates(RE_(3)Nb/TaO_(7)) stiffness(K) fracture toughness(KIC) thermal transports

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Distinct Evolution of the SST Anomalies in the Far Eastern Pacific between the 1997/98 and 2015/16 Extreme El Niños

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Advances in Atmospheric Sciences 2022年第6期39卷 927-942页

作者： Shaolei TANG Jing-Jia LUO lin chen Yongqiang YU Institute for Climate and Application Research(ICAR) Nanjing University of Information Science and TechnologyNanjing 210044China Key Laboratory of Meteorological Disaster Ministry of Education(KLME)/ILCEC/CIC-FEMDNanjing University of Information Science and TechnologyNanjing 210044China State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics(LASG) Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China University of Chinese Academy of Sciences Beijing 100049China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China

The 2015/16 El Niño displayed a distinct feature in the SST anomalies over the far eastern Pacific(FEP)compared to the 1997/98 extreme case.In contrast to the strong warm SST anomalies in the FEP in the 1997/98 event,the FEP warm SST anomalies in the 2015/16 El Niño were modest and accompanied by strong southeasterly wind anomalies in the southeastern Pacific.Exploring possible underlying causes of this distinct difference in the FEP may improve understanding of the diversity of extreme El Niños.Here,we employ observational analyses and numerical model experiments to tackle this issue.Mixed-layer heat budget analysis suggests that compared to the 1997/98 event,the modest FEP SST warming in the 2015/16 event was closely related to strong vertical upwelling,strong westward current,and enhanced surface evaporation,which were caused by the strong southeasterly wind anomalies in the southeastern Pacific.The strong southeasterly wind anomalies were initially triggered by the combined effects of warm SST anomalies in the equatorial central and eastern Pacific(CEP)and cold SST anomalies in the southeastern subtropical Pacific in the antecedent winter,and then sustained by the warm SST anomalies over the northeastern subtropical Pacific and CEP.In contrast,southeasterly wind anomalies in the 1997/98 El Niño were partly restrained by strong anomalously negative sea level pressure and northwesterlies in the northeast flank of the related anomalous cyclone in the subtropical South Pacific.In addition,the strong southeasterly wind and modest SST anomalies in the 2015/16 El Niño may also have been partly related to decadal climate variability.

关键词： El Nño-Southern Oscillation extreme El Niño El Niño diversity far eastern Pacific decadal climate variability

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Critical scale grain size for optimal lifetime of TBCs

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Journal of Materials Science & Technology 2022年第20期115卷 241-250页

作者： lin chen Guo-Hui Meng Chang-Jiu Li Guan-Jun Yang State Key Laboratory for Mechanical Behavior of Materials School of Materials Science and EngineeringXi’an Jiaotong UniversityXi’an 710049China

Thermal barrier coatings(TBCs)suffer from spalling failure resulting from the rapid growth of thermally grown oxides(TGO)on the metallic bond coat.In this study,to achieve the optimal lifetime of TBCs,a lifetime phase diagram was constructed for the entire service of TBCs.Herein,both the thermal mismatch stress during thermal cycling and the TGO growth stress during thermal exposure were considered.First,thickening behavior of the Al_(2)O_(3) scale related to grain size was investigated.Second,transverse delamination failure due to the thermal mismatch stress was analyzed.Third,vertical cracking failure related to early scale growth was explored.Finally,a critical scale grain size of~2.5μm was identified for achieving the optimal lifetime of TBCs.It was experimentally proved that vertical cracking of the Al_(2)O_(3) scale occurred during early oxidation as the scale grain size was larger than~4μm after pre-oxidation.The proposed lifetime phase diagram and critical scale grain size effect serve as novel criteria for the design of next-generation durable TBCs.

关键词： TGO growth Grain size Grain boundaries Channel cracking Service lifetime

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