The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are ...extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion.
What's new?
The tumor microenvironment (TME) is composed of heterogeneous tumor cells and host cells interacting with each other to promote disease progression. However, diagnostic and prognostic biomarkers to monitor the cancer stem cells (CSCs)‐host interplay are lacking. Here, the authors explore the role of tumor exosomes in cancer stemness and demonstrate that RAB27B‐assisted secretion of miRNA‐dominant exosomes is one critical feature of CSCs. Importantly, they show that colorectal cancer stem cells release miR‐146a‐loaded oncogenic exosomes for reprogramming non‐CSC cells and demonstrate the clinical relevance of exosomal miR‐146a in predicting the TME of CRC patients.
The Coronavirus disease 2019 (COVID-19) is an infectious disease presenting a major threat to public health. This study aims to assess Internet use characteristics and objectively examine the ...potential psychological factors associated with Internet addiction (IA) during the COVID-19 epidemic.
A cross-sectional, anonymized, self-reported survey was conducted among Chinese children and adolescents aged 6 to 18 years old. Participants completed questionnaires containing Young's Internet Addiction Test (IAT) and the Depression, Anxiety, and Stress Scale (DASS-21), and questions regarding demographic information and Internet use characteristics.
A total of 2050 participants (mean age:12.34 ± 4.67 years old, female: 48.44%) were enrolled. Fifty-five (2.68%) participants met the criterion for addictive Internet use (IAT≥70), while 684 (33.37%) participants were classified as problematic Internet users (69≥IAT≥40). Internet usage had grown during the COVID-19 epidemic, including the frequency and duration of recreational Internet use, and the frequency of stay-up Internet use. A linear regression analysis showed female gender (β=-0.091, p<0.001), age (β=0.066, p=0.001), depression (β=0.257, p<0.001), and stress (β=0.323, p<0.001) were significantly correlated with the IAT total scores (R=0.539, R
0.291, p<0.001).
We observed excessive Internet use among Chinese children and adolescents during the outbreak of COVID-19. Age, gender, depression, and stress were the potential key factors affecting IA. Extended family and professional support should be considered for vulnerable individuals during these unprecedented times.
Transition-metal-catalyzed decarbonylation via carbon-carbon bond cleavage is an essential synthetic methodology. Given the ubiquity of carbonyl compounds, the selective decarbonylative process ...offers a distinct synthetic strategy using carbonyl groups as "traceless handles". This reaction has been significantly developed in recent years in many respects, including catalytic system development, mechanistic understanding, substrate scope, and application in the synthesis of complex functional molecules. Therefore, this review aims to summarize the recent progress on transition-metal-catalyzed decarbonylative process, from the discovery of new transformations to the understanding of reaction mechanisms, to reveal the great achievements and potentials in this field. The contents of this review are categorized by the type of chemical bond cleavage in the decarbonylative process. The main challenges and opportunities of the decarbonylative process are also examined with the goal of expanding the application range of decarbonylation reactions.
Asymmetrical cell division (ACD) maintains the proper number of stem cells to ensure self-renewal. In cancer cells, the deregulation of ACD disrupts the homeostasis of the stem cell pool and promotes ...tumour growth. However, this mechanism is unclear. Here, we show a reduction of ACD in spheroid-derived colorectal cancer stem cells (CRCSCs) compared with differentiated cancer cells. The epithelial-mesenchymal transition (EMT) inducer Snail is responsible for the ACD-to-symmetrical cell division (SCD) switch in CRCSCs. Mechanistically, Snail induces the expression of microRNA-146a (miR-146a) through the β-catenin-TCF4 complex. miR-146a targets Numb to stabilize β-catenin, which forms a feedback circuit to maintain Wnt activity and directs SCD. Interference with the Snail-miR-146a–β-catenin loop by inhibiting the MEK or Wnt activity reduces the symmetrical division of CRCSCs and attenuates tumorigenicity. In colorectal cancer patients, the Snail(High)Numb(Low) profile is correlated with cetuximab resistance and a poorer prognosis. This study elucidates a unique mechanism of EMT-induced CRCSC expansion.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The homojunction of oxygen/metal vacancies and its interfacial n–p effect on the physiochemical properties are rarely reported. Interfacial n–p homojunctions of TiO2 are fabricated by directly ...decorating interfacial p‐type titanium‐defected TiO2 around n‐type oxygen‐defected TiO2 nanocrystals in amorphous–anatase homogeneous nanostructures. Experimental measurements and theoretical calculations on the cell lattice parameters show that the homojunction of oxygen and titanium vacancies changes the charge density of TiO2; a strong EPR signal caused by oxygen vacancies and an unreported strong titanium vacancies signal of 2D 1H TQ‐SQ MAS NMR are present. Amorphous–anatase TiO2 shows significant performance regarding the photogeneration current, photocatalysis, and energy storage, owing to interfacial n‐type to p‐type conductivity with high charge mobility and less structural confinement of amorphous clusters. A new “homojunction of oxygen and titanium vacancies” concept, characteristics, and mechanism are proposed at an atomic‐/nanoscale to clarify the generation of oxygen vacancies and titanium vacancies as well as the interface electron transfer.
The homojunction of oxygen and titanium vacancies developed in the amorphous–anatase interface of nanostructured TiO2 results in a unique n–p electronic transmission, which is mostly preferred to the mobility of electronic charge carriers. It also contributes to significant performance regarding photogeneration current, photocatalysis, and energy storage.
Polyimide (PI) aerogels have attracted great attention owing to their low density and excellent thermal stability. However, hydrophobic surface modification is required for PI aerogels to improve ...their ability in oil/water separation due to their amphiphilic characteristic. Two-dimensional MXenes (transition metal carbides/nitrides) can be utilized as nanofillers to enhance the properties of polymers because of their unique layered structure and versatile interface chemistry. Herein, the robust, lightweight, and hydrophobic PI/MXene three-dimensional architectures were fabricated via freeze-drying of polyamide acid/MXene suspensions and thermal imidization. Polyamide acid was synthesized using N-N-dimethylacetamide and 4,4′-oxydianiline. MXene (Ti3C2T x ) dispersion was obtained via the etching of Ti3AlC2 and ultrasonic exfoliation. Taking advantage of the strong interaction between PI chains and MXene nanosheets, the interconnected, highly porous, and hydrophobic PI/MXene aerogels with low density were fabricated, resulting in the improved compressive performance, remarkable oil absorption capacity, and efficient separation of oil and water. For the PI/MXene-3 aerogel (weight ratio, 5.2:1) without any surface modification, the water contact angle was 119° with a density of 23 mg/cm3. This aerogel can completely recover to its original height after 50 compression–release cycles, exhibiting superelasticity and exceptional fatigue-resistant ability. It also showed high absorption capacities to various organic liquids ranging from approximately 18 to 58 times of their own weight. This hybrid aerogel can rapidly separate the chloroform, soybean oil, and liquid paraffin from the water–oil system. The thermally stable hybrid aerogel also exhibited excellent fire safety properties and outstanding reusability under an extreme environment.
It has been reported that the biological functions of enzymes could be altered when they are encapsulated in metal–organic frameworks (MOFs) due to the interactions between them. Herein, we probed ...the interactions of catalase in solid and hollow ZIF-8 microcrystals. The solid sample with confined catalase is prepared through a reported method, and the hollow sample is generated by hollowing the MOF crystals, sealing freestanding enzymes in the central cavities of hollow ZIF-8. During the hollowing process, the samples were monitored by small-angle X-ray scattering (SAXS) spectroscopy, electron microscopy, powder X-ray diffraction (PXRD), and nitrogen sorption. The interfacial interactions of the two samples were studied by infrared (IR) and fluorescence spectroscopy. IR study shows that freestanding catalase has less chemical interaction with ZIF-8 than confined catalase, and a fluorescence study indicates that the freestanding catalase has lower structural confinement. We have then carried out the hydrogen peroxide degradation activities of catalase at different stages and revealed that the freestanding catalase in hollow ZIF-8 has higher activity.
Abstract
We report on the results of a new spectroscopic monitoring campaign of the quasar PG 0026+129 at the Calar Alto Observatory 2.2 m telescope from 2017 July to 2020 February. Significant ...variations in the fluxes of the continuum and broad emission lines, including H
β
and He
ii
, were observed in the first and third years, and clear time lags between them are measured. The broad H
β
line profile consists of two Gaussian components: an intermediate-width H
with an FWHM of 1964 ± 18
and another very broad H
with an FWHM of 7570 ± 83
. H
has long time lags of ∼40–60 days in the rest frame, while H
shows nearly zero time delay with respect to the optical continuum at 5100 Å. The velocity-resolved delays show consistent results: lags of ∼30–50 days at the core of the broad H
β
line and roughly zero lags at the wings. H
has a redshift of ∼400
, which seems to be stable for nearly 30 yr by comparing with archived spectra, and may originate from an infall. The rms spectrum of H
shows a double-peaked profile with brighter blue peak and extended red wing in the first year, which matches the signature of a thin disk. Both the double-peaked profile and the near-zero lag suggest that H
comes from a region associated with the part of the accretion disk that emits the optical continuum. Adopting the FWHM (in the rms spectrum) and the time lag measured for the total H
β
line, and a virial factor of 1.5, we obtain a virial mass of
for the central black hole in this quasar.
Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin ...receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.
Abstract
We report the results of a multiyear spectroscopic and photometric monitoring campaign of two luminous quasars, PG 0923+201 and PG 1001+291, both located at the high-luminosity end of the ...broad-line region (BLR) size–luminosity relation with optical luminosities above 10
45
erg s
−1
. PG 0923+201 is monitored for the first time, while PG 1001+291 was previously monitored but our campaign has a much longer temporal baseline. We detect time lags of variations of the broad H
β
, H
γ
, and Fe
ii
lines with respect to those of the 5100 Å continuum. The velocity-resolved delay map of H
β
in PG 0923+201 indicates a complicated structure with a mix of Keplerian disk-like motion and outflow, and the map of H
β
in PG 1001+291 shows a signature of Keplerian disk-like motion. Assuming a virial factor of
f
BLR
= 1 and FWHM line widths, we measure the black hole mass to be
118
−
16
+
11
×
10
7
M
⊙
for PG 0923+201 and
3.33
−
0.54
+
0.62
×
10
7
M
⊙
for PG 1001+291. Their respective accretion rates are estimated to be
0.21
−
0.07
+
0.06
×
L
Edd
c
−
2
and
679
−
227
+
259
×
L
Edd
c
−
2
, indicating that PG 0923+201 is a sub-Eddington accretor and PG 1001+291 is a super-Eddington accretor. While the H
β
time lag of PG 0923+201 agrees with the size–luminosity relation, the time lag of PG 1001+291 shows a significant deviation, confirming that in high-luminosity active galactic nuclei (AGNs), the BLR size depends on both luminosity and Eddington ratio. Black hole mass estimates from single-AGN spectra will be overestimated at high luminosities and redshifts if this effect is not taken into account.
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