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1.
Chem Commun (Camb) ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836703

ABSTRACT

Cobalt substitution for manganese sites in Na0.44MnO2 initiates a dynamic structural evolution process, yielding a composite cathode material comprising intergrown P2 and P3 phases. The novel P2/P3 composite cathode exhibits a reversible phase transition process during Na+ extraction/insertion, showcasing its attractive battery performance in sodium-ion batteries.

2.
ACS Nano ; 18(20): 12945-12956, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38717846

ABSTRACT

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

3.
BMC Genomics ; 25(1): 398, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654150

ABSTRACT

Pinellia ternata (Thunb.) Briet., a valuable herb native to China, is susceptible to the "sprout tumble" phenomenon because of high temperatures, resulting in a significant yield reduction. However, the molecular regulatory mechanisms underlying the response of P. ternata to heat stress are not well understood. In this study, we integrated transcriptome and miRNAome sequencing to identify heat-response genes, microRNAs (miRNAs), and key miRNA-target pairs in P. ternata that differed between heat-stress and room-temperature conditions. Transcriptome analysis revealed extensive reprogramming of 4,960 genes across various categories, predominantly associated with cellular and metabolic processes, responses to stimuli, biological regulation, cell parts, organelles, membranes, and catalytic and binding activities. miRNAome sequencing identified 1,597 known/conserved miRNAs that were differentially expressed between the two test conditions. According to the analysis, genes and miRNAs associated with the regulation of transcription, DNA template, transcription factor activity, and sequence-specific DNA binding pathways may play a major role in the resistance to heat stress in P. ternata. Integrated analysis of the transcriptome and miRNAome expression data revealed 41 high-confidence miRNA-mRNA pairs, forming 25 modules. MYB-like proteins and calcium-responsive transcription coactivators may play an integral role in heat-stress resistance in P. ternata. Additionally, the candidate genes and miRNAs were subjected to quantitative real-time polymerase chain reaction to validate their expression patterns. These results offer a foundation for future studies exploring the mechanisms and critical genes involved in heat-stress resistance in P. ternata.


Subject(s)
Heat-Shock Response , MicroRNAs , Pinellia , Seedlings , Transcriptome , Pinellia/genetics , Pinellia/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Heat-Shock Response/genetics , Seedlings/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant
4.
Chem Sci ; 15(14): 5192-5200, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38577355

ABSTRACT

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

5.
Chem Soc Rev ; 53(8): 4230-4301, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38477330

ABSTRACT

Sodium-ion batteries (SIBs) are experiencing a large-scale renaissance to supplement or replace expensive lithium-ion batteries (LIBs) and low energy density lead-acid batteries in electrical energy storage systems and other applications. In this case, layered oxide materials have become one of the most popular cathode candidates for SIBs because of their low cost and comparatively facile synthesis method. However, the intrinsic shortcomings of layered oxide cathodes, which severely limit their commercialization process, urgently need to be addressed. In this review, inherent challenges associated with layered oxide cathodes for SIBs, such as their irreversible multiphase transition, poor air stability, and low energy density, are systematically summarized and discussed, together with strategies to overcome these dilemmas through bulk phase modulation, surface/interface modification, functional structure manipulation, and cationic and anionic redox optimization. Emphasis is placed on investigating variations in the chemical composition and structural configuration of layered oxide cathodes and how they affect the electrochemical behavior of the cathodes to illustrate how these issues can be addressed. The summary of failure mechanisms and corresponding modification strategies of layered oxide cathodes presented herein provides a valuable reference for scientific and practical issues related to the development of SIBs.

6.
Plant Physiol Biochem ; 208: 108539, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38513515

ABSTRACT

Pinellia ternata, a valuable Chinese herb, suffers yield reduction due to "sprout tumble" under high temperatures. However, the mechanisms underlying its high-temperature stress remain poorly understood. NAM, ATAF1/2, and CUC2 (NAC) transcription factors regulate plant tissue growth and abiotic stress. Hence, there has been no comprehensive research conducted on NAC transcription factors in P. ternata. We identified 98 PtNAC genes unevenly distributed across 13 chromosomes, grouped into 15 families via phylogenetic analysis. Gene expression analysis revealed diverse expression patterns of PtNAC genes in different tissue types. Further studies revealed that PtNAC5/7/17/35/43/47/57/66/86 genes were highly expressed in various tissues of P. ternata and induced by heat stress, among which PtNAC66 was up-regulated at the highest folds induced by heat temperature. PtNAC66 is a nuclear protein that can selectively bind to the cis-responsive region NACRS but lacks the ability to activate transcription in yeast. For further research, PtNAC66 was cloned and transgenic Arabidopsis was obtained. PtNAC66 overexpression increased high-temperature tolerance compared to wild-type plants. Transcriptome profiling demonstrated that overexpression of PtNAC66 led to significant modification of genes responsible for regulating binding, catalytic activity, transcription regulator activity and transporter activity response genes. Additionally, PtNAC66 was found to bind the promoters of CYP707A3, MYB102 and NAC055, respectively, and inhibited their expression, affecting the high-temperature stress response in Arabidopsis. Our research established the foundation for functional studies of PtNAC genes in response to high-temperature forcing by characterizing the P. ternata NAC gene family and examining the biological role of PtNAC66 in plant high-temperature tolerance.


Subject(s)
Arabidopsis , Pinellia , Transcription Factors/genetics , Transcription Factors/metabolism , Arabidopsis/metabolism , Pinellia/genetics , Pinellia/metabolism , Temperature , Phylogeny , Stress, Physiological/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism
7.
Ophthalmic Res ; 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38555640

ABSTRACT

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

8.
Funct Plant Biol ; 512024 02.
Article in English | MEDLINE | ID: mdl-38316513

ABSTRACT

Pinellia ternata is an important natural medicinal herb in China. However, it is susceptible to withering when exposed to high temperatures during growth, which limits its tuber production. Mitochondria usually function in stress response. The P . ternata mitochondrial (mt) genome has yet to be explored. Therefore, we integrated PacBio and Illumina sequencing reads to assemble and annotate the mt genome of P . ternata . The circular mt genome of P . ternata is 876 608bp in length and contains 38 protein-coding genes (PCGs), 20 tRNA genes and three rRNA genes. Codon usage, sequence repeats, RNA editing and gene migration from chloroplast (cp) to mt were also examined. Phylogenetic analysis based on the mt genomes of P . ternata and 36 other taxa revealed the taxonomic and evolutionary status of P . ternata . Furthermore, we investigated the mt genome size and GC content by comparing P . ternata with the other 35 species. An evaluation of non-synonymous substitutions and synonymous substitutions indicated that most PCGs in the mt genome underwent negative selection. Our results provide comprehensive information on the P . ternata mt genome, which may facilitate future research on the high-temperature response of P . ternata and provide new molecular insights on the Araceae family.


Subject(s)
Genome, Mitochondrial , Pinellia , Plants, Medicinal , Pinellia/genetics , Genome, Mitochondrial/genetics , Phylogeny , Plants, Medicinal/genetics , Plant Tubers
9.
Adv Mater ; 36(16): e2311814, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38194156

ABSTRACT

Li-rich cathode materials have emerged as one of the most prospective options for Li-ion batteries owing to their remarkable energy density (>900 Wh kg-1). However, voltage hysteresis during charge and discharge process lowers the energy conversion efficiency, which hinders their application in practical devices. Herein, the fundamental reason for voltage hysteresis through investigating the O redox behavior under different (de)lithiation states is unveiled and it is successfully addressed by formulating the local environment of O2-. In Li-rich Mn-based materials, it is confirmed that there exists reaction activity of oxygen ions at low discharge voltage (<3.6 V) in the presence of TM-TM-Li ordered arrangement, generating massive amount of voltage hysteresis and resulting in a decreased energy efficiency (80.95%). Moreover, in the case where Li 2b sites are numerously occupied by TM ions, the local environment of O2- evolves, the reactivity of oxygen ions at low voltage is significantly inhibited, thus giving rise to the large energy conversion efficiency (89.07%). This study reveals the structure-activity relationship between the local environment around O2- and voltage hysteresis, which provides guidance in designing next-generation high-performance cathode materials.

11.
Adv Mater ; 36(15): e2307938, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37910130

ABSTRACT

Layered oxides have become the research focus of cathode materials for sodium-ion batteries (SIBs) due to the low cost, simple synthesis process, and high specific capacity. However, the poor air stability, unstable phase structure under high voltage, and slow anionic redox kinetics hinder their commercial application. In recent years, the concept of manipulating orbital hybridization has been proposed to simultaneously regulate the microelectronic structure and modify the surface chemistry environment intrinsically. In this review, the hybridization modes between atoms in 3d/4d transition metal (TM) orbitals and O 2p orbitals near the region of the Fermi energy level (EF) are summarized based on orbital hybridization theory and first-principles calculations as well as various sophisticated characterizations. Furthermore, the underlying mechanisms are explored from macro-scale to micro-scale, including enhancing air stability, modulating high working voltage, and stabilizing anionic redox chemistry. Meanwhile, the origin, formation conditions, and different types of orbital hybridization, as well as its application in layered oxide cathodes are presented, which provide insights into the design and preparation of cathode materials. Ultimately, the main challenges in the development of orbital hybridization and its potential for the production application are also discussed, pointing out the route for high-performance practical sodium layered oxide cathodes.

12.
Small ; 20(11): e2306690, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37926792

ABSTRACT

Non-aqueous solvents, in particular N,N-dimethylaniline (NMP), are widely applied for electrode fabrication since most sodium layered oxide cathode materials are readily damaged by water molecules. However, the expensive price and poisonousness of NMP unquestionably increase the cost of preparation and post-processing. Therefore, developing an intrinsically stable cathode material that can implement the water-soluble binder to fabricate an electrode is urgent. Herein, a stable nanosheet-like Mn-based cathode material is synthesized as a prototype to verify its practical applicability in sodium-ion batteries (SIBs). The as-prepared material displays excellent electrochemical performance and remarkable water stability, and it still maintains a satisfactory performance of 79.6% capacity retention after 500 cycles even after water treatment. The in situ X-ray diffraction (XRD) demonstrates that the synthesized material shows an absolute solid-solution reaction mechanism and near-zero-strain. Moreover, the electrochemical performance of the electrode fabricated with a water-soluble binder shows excellent long-cycling stability (67.9% capacity retention after 500 cycles). This work may offer new insights into the rational design of marvelous water stability cathode materials for practical SIBs.

13.
Chem Sci ; 14(47): 13924-13933, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38075638

ABSTRACT

Ni-rich cathodes with a radial ordered microstructure have been proved to enhance materials' structural stability. However, the construction process of radial structures has not yet been clearly elaborated. Herein, the formation process of radial structures induced by different doped elements has been systematically investigated. The advanced Electron Back Scatter Diffraction (EBSD) characterization reveals that W-doped materials are more likely to form a low-angle arrangement between crystal planes of the primary particles and exhibit twin growth during sintering than a B-doped cathode. The corresponding High Angle Annular Dark Field-Scanning Transmission Electron Microscopy (HAADF-STEM) analysis further proves that the twin growth induced by W doping can promote the migration of Li+. Simultaneously, the W-doped sample reduces the (003) plane surface energy and promotes the retention of the crystal plane, which can effectively alleviate the structural degradation caused by Li+ (de)intercalation. At a cut-off voltage of 4.6 V, the W-doped cathode displays a capacity retention rate of 94.1% after 200 cycles at 1C. This work unveils the influence of different element doping on the structure from the perspective of crystal plane orientation within primary particles and points out the importance of the exposure and orientation of the crystal plane of the particles.

14.
Sci Adv ; 9(51): eadj1397, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38117877

ABSTRACT

Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor-mediated apoptosis promote gasdermin E (GSDME)-dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.


Subject(s)
Extracellular Traps , Neutrophils , Neutrophils/metabolism , Protein-Arginine Deiminases/genetics , Protein-Arginine Deiminases/metabolism , Protein-Arginine Deiminase Type 4/genetics , Protein-Arginine Deiminase Type 4/metabolism , Extracellular Traps/genetics , Extracellular Traps/metabolism , Histones/metabolism , Epigenesis, Genetic
15.
Front Immunol ; 14: 1224045, 2023.
Article in English | MEDLINE | ID: mdl-38022639

ABSTRACT

Purpose: Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage. Experimental design: Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning. Results: We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis. Conclusion: Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Melanoma , Humans , Neutrophils , Antigens, CD19 , B-Lymphocytes
16.
Front Biosci (Landmark Ed) ; 28(9): 202, 2023 09 14.
Article in English | MEDLINE | ID: mdl-37796682

ABSTRACT

BACKGROUND: High temperature and drought environments are important limiting factors for Pinellia ternata growth, whereas shading can promote growth by relieving these stresses. However, the mechanism of growth promotion by shading in P. ternata is unknown. Long non-coding RNAs (lncRNAs) play important roles in the plant's growth and environmental response, but few analyses of lncRNAs in P. ternata have been reported. METHODS: We performed lncRNAs analysis of P. ternata in response to shading using RNA-seq data from our previous studies. A total of 13,927 lncRNAs were identified, and 145 differentially expressed lncRNAs (DELs) were obtained from the comparisons of 5 days shade (D5S) vs. 5 days of natural light (D5CK), 20 days of shade (D20S) vs. 20 days of natural light (D20CK), D20S vs. D5S, and D20CK vs. D5CK. Of these, 119 DELs (82.07%) were generated from the D20S vs. D20CK comparison. RESULTS: Gene ontology (GO) analysis indicated that the reactive oxygen (ROS) metabolism and programmed cell death (PCD) processes might regulate shade-induced growth promotion. The "signal transduction" and "environmental adaptation" in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for lncRNA-mRNA regulatory network construction and showed that the lncRNAs might mediate P. ternata growth by regulating ROS accumulation and light signals. CONCLUSIONS: This study explores lncRNAs' functions and regulatory mechanisms related to P. ternata growth and lays a foundation for further research on P. ternata.


Subject(s)
Pinellia , RNA, Long Noncoding , Pinellia/genetics , Pinellia/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Reactive Oxygen Species/metabolism , Gene Expression Profiling
17.
ACS Appl Mater Interfaces ; 15(38): 44839-44847, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37694844

ABSTRACT

Manganese-based layered oxides are prospective cathode materials for sodium-ion batteries (SIBs) due to their low cost and high theoretical capacities. The biphasic intergrowth structure of layered cathode materials is essential for improving the sodium storage performance, which is attributed to the synergistic effect between the two phases. However, the in-depth formation mechanism of biphasic intergrowth materials remains unclear. Herein, the layered/tunnel intergrowth Na0.6MnO2 (LT-NaMO) as a model material was successfully prepared, and their formation processes and electrochemical performance were systematically investigated. In situ high-temperature X-ray diffraction displays the detailed evolution process and excellent thermal stability of the layered/tunnel intergrowth structure. Furthermore, severe structural strain and large lattice volume changes are significantly mitigated by the interlocking effect between the phase interfaces, which further enhances the structural stability of the cathode materials during the charging/discharging process. Consequently, the LT-NaMO cathode displays fast Na+ transport kinetics with a remarkable capacity retention of ∼70.5% over 300 cycles at 5C, and its assembled full cell with hard carbon also exhibits high energy density. These findings highlight the superior electrochemical performance of intergrowth materials due to interlocking effects between layered and tunnel structures and also provide unique insights into the construction of intergrowth cathode materials for SIBs.

18.
Adv Mater ; 35(40): e2305149, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37528535

ABSTRACT

Optimizing charge transfer and alleviating volume expansion in electrode materials are critical to maximize electrochemical performance for energy-storage systems. Herein, an atomically thin soft-rigid Co9 S8 @MoS2 core-shell heterostructure with dual cation vacancies at the atomic interface is constructed as a promising anode for high-performance sodium-ion batteries. The dual cation vacancies involving VCo and VMo in the heterostructure and the soft MoS2 shell afford ionic pathways for rapid charge transfer, as well as the rigid Co9 S8 core acting as the dominant active component and resisting structural deformation during charge-discharge. Electrochemical testing and theoretical calculations demonstrate both excellent Na+ -transfer kinetics and pseudocapacitive behavior. Consequently, the soft-rigid heterostructure delivers extraordinary sodium-storage performance (389.7 mA h g-1 after 500 cycles at 5.0 A g-1 ), superior to those of the single-phase counterparts: the assembled Na3 V2 (PO4 )3 ||d-Co9 S8 @MoS2 /S-Gr full cell achieves an energy density of 235.5 Wh kg-1 at 0.5 C. This finding opens up a unique strategy of soft-rigid heterostructure and broadens the horizons of material design in energy storage and conversion.

19.
ACS Nano ; 17(16): 15871-15882, 2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37526621

ABSTRACT

Due to their high capacity and sufficient Na+ storage, O3-NaNi0.5Mn0.5O2 has attracted much attention as a viable cathode material for sodium-ion batteries (SIBs). However, the challenges of complicated irreversible multiphase transitions, poor structural stability, low operating voltage, and an unstable oxygen redox reaction still limit its practical application. Herein, using O3-NaNi0.5Mn0.5-xSnxO2 cathode materials as the research model, a universal strategy based on bridging microstructure engineering and local electronic structure manipulation is proposed. The strategy can modulate the physical and chemical properties of electrode materials, so as to restrain the unfavorable and irreversible multiphase transformation, improve structural stability, manipulate redox potential, and stabilize the anion redox reaction. The effect of Sn substitution on the intrinsic local electronic structure of the material is articulated by density functional theory calculations. Meanwhile, the universal strategy is also validated by Ti substitution, which could be further extrapolated to other systems and guide the design of cathode materials in the field of SIBs.

20.
Front Immunol ; 14: 1101497, 2023.
Article in English | MEDLINE | ID: mdl-37426658

ABSTRACT

CD8+ T cells drive anti-cancer immunity in response to antigen-presenting cells such as dendritic cells and subpopulations of monocytes and macrophages. While CD14+ classical monocytes modulate CD8+ T cell responses, the contributions of CD16+ nonclassical monocytes to this process remain unclear. Herein we explored the role of nonclassical monocytes in CD8+ T cell activation by utilizing E2-deficient (E2-/-) mice that lack nonclassical monocytes. During early metastatic seeding, modeled by B16F10-OVA cancer cells injected into E2-/- mice, we noted lower CD8+ effector memory and effector T cell frequencies within the lungs as well as in lung-draining mediastinal lymph nodes in the E2-/- mice. Analysis of the myeloid compartment revealed that these changes were associated with depletion of MHC-IIloLy6Clo nonclassical monocytes within these tissues, with little change in other monocyte or macrophage populations. Additionally, nonclassical monocytes preferentially trafficked to primary tumor sites in the lungs, rather than to the lung-draining lymph nodes, and did not cross-present antigen to CD8+ T cells. Examination of the lung microenvironment in E2-/- mice revealed reduced CCL21 expression in endothelial cells, which is chemokine involved in T cell trafficking. Our results highlight the previously unappreciated importance of nonclassical monocytes in shaping the tumor microenvironment via CCL21 production and CD8+ T cell recruitment.


Subject(s)
Monocytes , Neoplasms , Mice , Animals , CD8-Positive T-Lymphocytes , Endothelial Cells , Lung , Neoplasms/metabolism , Tumor Microenvironment
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