Abstract
The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have ...been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell tri-cell co-culture system, neutrophils are shown to potentially suppress the tumoricidal activity of NK cells, while neutrophils themselves are tumoricidal. Intriguingly, these two modulatory effects by neutrophils are both mediated by reactive oxygen species. Collectively, the absence or presence of NK cells, governs the net tumor-modulatory effects of neutrophils.
Acquisition of a lipid-laden phenotype by immune cells has been defined in infectious diseases and atherosclerosis but remains largely uncharacterized in cancer. Here, in breast cancer models, we ...found that neutrophils are induced to accumulate neutral lipids upon interaction with resident mesenchymal cells in the premetastatic lung. Lung mesenchymal cells elicit this process through repressing the adipose triglyceride lipase (ATGL) activity in neutrophils in prostaglandin E2-dependent and -independent manners. In vivo, neutrophil-specific deletion of genes encoding ATGL or ATGL inhibitory factors altered neutrophil lipid profiles and breast tumor lung metastasis in mice. Mechanistically, lipids stored in lung neutrophils are transported to metastatic tumor cells through a macropinocytosis-lysosome pathway, endowing tumor cells with augmented survival and proliferative capacities. Pharmacological inhibition of macropinocytosis significantly reduced metastatic colonization by breast tumor cells in vivo. Collectively, our work reveals that neutrophils serve as an energy reservoir to fuel breast cancer lung metastasis.
Ag-modified CF
x
cathode material was prepared via a redox process using hydrated hydrazine as the reducing agent and silver nitrate as the Ag source, respectively. Pouch Li/Ag-CF
x
batteries with ...capacity of 2 Ah were prepared using Ag-CF
x
as the active material for the cathode and lithium flakes for the anode. The phase composition, morphology features and elemental distribution of the Ag-CF
x
material were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM) and x-ray diffraction (EDS), respectively. The effect of Ag doping on the electrochemical properties of the Ag-CF
x
cathode was also investigated. The results showed that the Li/5%Ag-CF
x
battery possessed the best electrochemical properties of all the obtained batteries, indicating capacity of 2.10 Ah at 0.05 C and plateau voltage of 2.581 V. The batteries showed capacity of 2.03 Ah and 1.99 Ah at 0.5 C and 1.0 C, respectively. The lowest temperature rise on the Li/Ag-CF
x
battery surface (10 Ah) with the 0.5%Ag-CF
x
cathode was 25.2°C at 1 C rate during discharge.
Intracellular cytokine staining (ICS) is a widely employed
method for quantitative determination of the activation status of immune cells, most often applied to T cells. ICS test samples are commonly ...prepared from animal or human tissues as unpurified cell mixtures, and cell-specific cytokine signals are subsequently discriminated by gating strategies using flow cytometry. Here, we show that when ICS samples contain Ly6G
neutrophils, neutrophils are
activated by an ICS reagent - phorbol myristate acetate (PMA) - which leads to hydrogen peroxide (H
O
) release and death of cytokine-expressing T cells. This artifact is likely to result in overinterpretation of the degree of T cell suppression, misleading immunological research related to cancer, infection, and inflammation. We accordingly devised easily implementable improvements to the ICS method and propose alternative methods for assessing or confirming cellular cytokine expression.
, belonging to the cold-specialized lineage Betulaceae, exhibits a unique reproductive strategy where staminate catkins emerge in the first summer and undergo an overwintering process, culminating in ...flowering in the following year. However, the underlying regulatory mechanism remains unclear. In this study, we investigated the male germline development of
in four distinct stages: microsporocytes in Oct. (S1), uninuclear microspores from Dec. (S2) to Mar. of the following year (S3), and bicellular microspores in Apr. (S4). We performed RNA sequencing on mature pollen and the four stages of staminate catkins. Using weighted gene co-expression network analysis (WGCNA), we identified five highly correlated gene modules with distinct expression profiles. These modules exhibited strong correlations with sugar metabolism, cell cycle, flowering, and cell wall dynamics, highlighting their dynamic roles during male germline developmental stages. During the overwintering process, we observed that the expression of transcription factors such as
and
at the appropriate developmental stages, suggests their significant roles in male germline development. The expression patterns of
and
suggest their potential involvement in temperature perception during male reproductive development. These findings offer valuable insights into the reproductive success of plants adapting to cold environments.
LiNi
0.8
Co
0.2−
x
Ti
x
O
2
cathode materials with different titanium (Ti) contents have been prepared from Ni
0.8
Co
0.2−
x
Ti
x
(OH)
2
(0 ≤
x
≤ 0.05) precursors. Phase and morphology analyses ...indicated that the products were microspheres in space group
R
3
¯
m
assembled from smaller secondary particles. Phase and elemental analyses indicated more serious cation mixing in the layered materials obtained with Ti doping. The LiNi
0.8
Co
0.2−
x
Ti
x
O
2
material with
x
= 0.0125 showed optimal electrochemical performance with improved cycling performance (capacity retention ratio of 95.8% after 100 cycles) and high rate capability (162 mAh g
−1
at 2C). Therefore, Ti doping can be considered an efficient approach to improve the electrochemical properties of such cathode materials.
Intrinsic stress response pathways are frequently mobilized within tumor cells. The mediators of these adaptive mechanisms and how they contribute to carcinogenesis remain poorly understood. A ...striking example is heat shock factor 1 (HSF1), master transcriptional regulator of the heat shock response. Surprisingly, we found that loss of the tumor suppressor gene neurofibromatosis type 1 (Nf1) increased HSF1 levels and triggered its activation in mouse embryonic fibroblasts. As a consequence, Nf1-/- cells acquired tolerance to proteotoxic stress. This activation of HSF1 depended on dysregulated MAPK signaling. HSF1, in turn, supported MAPK signaling. In mice, Hsf1 deficiency impeded NF1-associated carcinogenesis by attenuating oncogenic RAS/MAPK signaling. In cell lines from human malignant peripheral nerve sheath tumors (MPNSTs) driven by NF1 loss, HSF1 was overexpressed and activated, which was required for tumor cell viability. In surgical resections of human MPNSTs, HSF1 was overexpressed, translocated to the nucleus, and phosphorylated. These findings reveal a surprising biological consequence of NF1 deficiency: activation of HSF1 and ensuing addiction to this master regulator of the heat shock response. The loss of NF1 function engages an evolutionarily conserved cellular survival mechanism that ultimately impairs survival of the whole organism by facilitating carcinogenesis.
In Brassicaceae, the papillary cells of the stigma are the primary site of the self-incompatibility (SI) responses. SI preserves the genetic diversity by selectively rejecting irrelevant or ...incompatible pollen, thus promoting cross fertilization and species fitness. Mechanisms that regulate SI responses in Brassica have been studied mainly on the mature stigma that often undermines how stigma papillary cells attain the state of SI during development. To understand this, we integrated PacBio SMRT-seq with Illumina RNA-seq to construct a de novo full-length transcriptomic database for different stages of stigma development in ornamental kale. A total of 48,800 non-redundant transcripts, 31,269 novel transcripts, 24,015 genes, 13,390 alternative splicing, 22,389 simple sequence repeats, 21,816 complete ORF sequences, and 4591 lncRNAs were identified and analyzed using PacBio SMRT-seq. The Illumina RNA-seq revealed 15,712 differentially expressed genes (DEGs) and 8619 transcription factors. The KEGG enrichment analysis of 4038 DEGs in the “incompatibility” group revealed that the flavonoid and fatty acid biosynthesis pathways were significantly enriched. The cluster and qRT-PCR analysis indicated that 11 and 14 candidate genes for the flavonoid and fatty acid biosynthesis pathways have the lowest expression levels at stigma maturation, respectively. To understand the physiological relevance of the downregulation of fatty acid biosynthesis pathways, we performed inhibitor feeding assays on the mature stigma. The compatible pollination response was drastically reduced when mature stigmas were pre-treated with a fatty acid synthase inhibitor. This finding suggested that fatty acid accumulation in the stigmas may be essential for compatible pollination and its downregulation during maturity must have evolved as a support module to discourage the mounting of self-incompatible pollen.
The hierarchically lithiated MoO3 microspheres composed of primary crystallized particles have been prepared in the absence of surfactant. The surface morphologies of the lithiated MoO3 structures ...can be well regulated through adjusting the adding amounts of ethanol during their synthetic process. The results of XRD patterns and the elemental analysis indicated the decrease of lithium content with the increase of ethanol feeding amount. The obtained lithiated MoO3 samples showed the initial capacities of nearly 300 mAh/g at 30 mA/g and 41.8 mAh/g at 200 mA/g. Therefore, this work has showed a facile way to fabricate the lithiated MoO3 cathode materials with controllable surface morphology and lithium content.
In this study, immobilized microbial beads were proposed as a solution for excessive nitrogen concentration of the river sediment. The predominant denitrifying microbes were screened from the river ...sediment. The optimized production of immobilized microbial beads and long-term nitrogen removal efficiency were investigated. 16S rRNA gene sequencing analysis showed that denitrifying bacteria such as Pseudomonas, Alcaligenes, Proteiniclasticum, Achromobacter and Methylobacillus were dominant microflora in the enriched microbial agent, which accounted for 94.43% of the total microbes. Pseudomonas belongs to Gammaproteo bacteria, accounting for 49.22% and functioned as the most predominant denitrifying bacteria. The material concentration of 8% polyvinyl alcohol, 0.5% sodium alginate and 12.5% microbial biomass were found to be the optimal immobilizing conditions. The NH4+-N and total nitrogen (TN) removal rates in sediment with dosing immobilized microbial beads were estimated as 68.1% and 67.8%, respectively, when compared to the dosing liquid microbial agent were 50.5% and 49.3%. Meanwhile, the NH4+-N and TN removal rates in overlying water went up from 53.14% to 59.69% and from 68.03% to 78.13%, respectively, by using immobilized microbial beads.
PDF
