Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The fundamental features of one kind of rarely known stratocumulus, which was termed as “Millipede Cloud,” occurred over the Eastern Pacific Ocean in 2017 were first documented by using Moderate ...Resolution Imaging Spectroradiometer (MODIS) satellite imagery. These clouds had long and meandering “central axes” extending from several hundreds to thousands kilometers, and a number of “radical cloud arms” extending several tens of kilometers in its two sides. Total 59 “Millipede Clouds,” 4 and 55 of them, were formed over the Northern and the Southern Hemispheres, respectively. Their environmental backgrounds were analyzed by using ERA5 reanalysis data and MODIS sensor Level‐2 data. The cloud top pressures of these “Millipede Clouds” were between 850 and 800 hPa, and their top heights were about 1–2 km. There existed “inversion layer” of air temperature near the cloud tops at 800 hPa, which strongly suggested that these clouds were lower stratocumulus in essence.
Plain Language Summary
“Millipede Cloud,” one kind of rarely known stratocumulus which looks like “Millipede” shape, is termed for the first time in this paper. It has an obvious “central axis” and a number of well‐organized “radial cloud arms” in two sides of the “central axis” extending in several tens of kilometers length. This paper introduces the fundamental features of “Millipede Clouds” occurred over the Eastern Pacific Ocean in 2017 from the perspective of satellite image. Totally, 59 “Millipede Clouds” were found to occur over the Eastern Pacific Ocean. Their geographic distribution, cloud top features and vertical structure of one typical case on 16 July 2017 were documented.
Key Points
The fundamental features of “Millipede Clouds” over the Eastern Pacific Ocean in 2017 were documented by using Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery
The environmental backgrounds of these “Millipede Clouds” were analyzed by using ERA5 reanalysis data and MODIS data
The cloud top pressures of these “Millipede Clouds” are between 850 and 800 hPa, and their top heights are about 1–2 km
Phase-change memory takes advantage of the fast phase transition between amorphous and crystalline phases of phase-change materials (
e.g.
, Ge
2
Sb
2
Te
5
or GST). To date, while the "SET" process ...(crystallization of GST glass) has been intensively studied, studies on the "RESET" process (melt-quenching amorphization of GST) are still limited. In this work, we explored the structural changes of GST upon rapid cooling by
ab initio
molecular dynamics simulations and atomistic cluster alignment (ACA) analysis. Different from other methods which only focus on the nearest bonding atoms, the ACA method can study both the short- and medium-range order clusters containing atoms beyond the first-neighboring shell and enables us to explore the changes of cluster structures in a larger scale. The results reveal that low-coordinated octahedral clusters tend to become high-coordinated ones, and Ge-centered octahedral structures change to tetrahedrons whereas Sb-centered tetrahedrons transform to octahedral structures during the amorphization process. Interestingly, tetrahedrons show aggregation in liquid and supercooled liquid in contrast to 6-fold octahedrons which present notable aggregation in amorphous GST. Moreover, our study showed that wrong bonds (Ge-Ge, Sb-Sb, Ge-Sb and Te-Te bonds) can promote the formation of large rings, and irreducible rings tend to separate into smaller and larger rings as the temperature is decreased. Our findings provide useful insights into the formation process and the structure of amorphous GST, which is valuable for facilitating the application of phase change materials.
Five structures (a tetrahedron and 3-, 4-, 5- and 6-fold octahedrons) are shown in the upper panel of the figure. Figures in the lower panel show the fractions of the five structures in Ge- and Sb-centered clusters with temperature.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
Crystalline Sb
2
Te
3
is widely studied due to its important applications in memory materials and topological insulators. The liquid and amorphous structures of this compound as well as the dynamics ...upon quenching, however, are yet to be fully understood. In this work, we have systematically studied the dynamical properties and local structure of Sb
2
Te
3
at different temperatures using
ab initio
molecular dynamics simulations. The calculated structure factors agree well with the experimental results. The atomic number density and mean-squared displacement as a function of temperature clearly indicate three states as the temperature decreases, namely, melt, undercooled liquid and glass state, respectively. By analyzing the chemical environments and bond-angle distribution functions, we demonstrate that the most probable short-range motifs in the Sb
2
Te
3
system are defective octahedrons, and they are connected with each other
via
four-fold rings. This interesting structural feature may be responsible for the high fragility and easy phase transition upon glass forming that is applied in memory devices.
Sb-centered defective octahedrons connect with each other
via
four-fold rings, a close link of the four-fold ring and defective octahedrons in amorphous Sb
2
Te
3
has been revealed.
Abstract
We present a spectral study of the black hole candidate MAXI J1348−630 during its 2019 outburst, based on monitoring observations with Insight-HXMT and Swift. Throughout the outburst, the ...spectra are well fitted with power-law plus disk-blackbody components. In the soft-intermediate and soft states, we observed the canonical relation
L
∝
T
in
4
between disk luminosity
L
and peak color temperature
T
in
, with a constant inner radius
R
in
(traditionally identified with the innermost stable circular orbit). At other stages of the outburst cycle, the behavior is more unusual, inconsistent with the canonical outburst evolution of black hole transients. In particular, during the hard rise, the apparent inner radius is smaller than in the soft state (and increasing), and the peak color temperature is higher (and decreasing). This anomalous behavior is found even when we model the spectra with self-consistent Comptonization models, which take into account the upscattering of photons from the disk component into the power-law component. To explain both anomalous trends at the same time, we suggest that the hardening factor for the inner-disk emission was larger than the canonical value of ≈1.7 at the beginning of the outburst. A more physical trend of radii and temperature evolution requires a hardening factor evolving from ≈3.5 at the beginning of the hard state to ≈1.7 in the hard-intermediate state. This could be evidence that the inner disk was in the process of condensing from the hot, optically thin medium and had not yet reached a sufficiently high optical depth for its emission spectrum to be described by the standard optically thick disk solution.
•A facile route was developed to fabricate Co3O4@NMC OER/ORR catalysts.•Co3O4@NMC (1:3) exhibits a considerable ORR/OER activity and stability.•Accelerated kinetic charge transfer process is the main ...reason for catalysis.
A nanocomposite with mesoporous Co3O4 loaded on nitrogen-doped mesoporous carbon (Co3O4@NMC) has been constructed by a facile post-grinding process. The electro-catalytic experimental results show that Co3O4@NMC (1:3) can be regarded as the low-cost alternative ORR/OER bi-functional catalyst compared with commercial noble Pt/C + IrO2 catalysts. The potential difference (ΔE) between between E1/2 and Ej10 for Co3O4@NMC (1:3) sample is only 21 mV larger. Moreover, we observed no obvious degeneration in both ORR and OER activity during ADT tests. The enhancement of electro-catalytic activity can be attributed to the effective charge transfer process as suggested by the Tafel analysis due to the synergistic effect.
MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures ...have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real‐time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti‐/pre‐miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR‐7, miR‐194 and miR‐449b, or overexpressing miR‐204, repressed migration, invasion and extracellular matrix‐adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR‐204, and two binding sites in the 3′‐untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR‐204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR‐204‐FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression‐ and metastasis‐related miRNAs offers a novel potential therapeutic strategy for the disease.
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